<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 Rachischisis and can you explain it in depth? [/INST] Rachischisis (Greek: "rhachis - ῥάχις" - spine, and "schisis - σχίσις" - split) is a developmental birth defect involving the neural tube. This anomaly occurs in utero, when the posterior neuropore of the neural tube fails to close by the 27th intrauterine day.  As a consequence the vertebrae overlying the open portion of the spinal cord do not fully form and remain unfused and open, leaving the spinal cord exposed.  Patients with rachischisis have motor and sensory deficits, chronic infections, and disturbances in bladder function.  This defect often occurs with anencephaly.
Craniorachischisis is a variant of rachischisis that occurs when the entire spinal cord and brain are exposed – simultaneous complete rachischisis and anencephaly. It is incompatible with life; affected pregnancies often end in miscarriage or stillbirth. Infants born alive with craniorachischisis die soon after birth.

Presentation
Interactions with other developmental deformities
Rachischisis is a complex condition and presents itself along with other deformities. Other deformities are typically those of the face, neck, spine and head. It is extremely common for rachischisis to develop in conjunction with aplasia (a condition in which a tissue or organ does not develop fully).Acrania is a developmental defect in which the bones with the cranial vault do not develop correctly and brain does not develop fully. Rachischisis can develop in conjunction with acrania, causing further damage to the brain and spinal regions. In the absence of acrania, patients with rachischisis still have a high mortality rate.Anencephaly is a condition in which the baby develops with an open skull in some region. Rachischisis can develop in conjunction with anencephaly, increasing the amount of area that is exposed. Although these conditions closely resemble one another, cases of rachischisis are morphologically different from cases of anencephaly, so they are indeed two separate conditions.
Rachischisis is also a contributing factor to the onset of iniencephaly – a condition in which the spine is malformed.
Further abnormalities such as rib malformations can occur with rachischisis. Stomach deformities can also develop with rachischisis.

Risk factors
If a sibling of the fetus has been affected by rachischisis, there is increased risk that another child will develop the condition. There is also a slightly higher chance that females will develop the condition over males.Folate deficiency is also a well-accepted risk factor of all neural tube defects, including rachischisis. It is this reason that has caused many health policies regarding folic acid during pregnancy to be developed.

Diagnosis
Initial diagnosis is typically by ultrasonography to reveal any congenital abnormalities. Fetuses affected typically show cranial abnormalities and deformities in brain tissue as well as spinal abnormalities. Following ultrasonography, magnetic resonance imaging (MRI) is commonly used to confirm the diagnosis. The presence of rachischisis is indicated in imaging by the absence of an arch-cranial line.Other neural tube defect diagnostic tools such as assays of α-fetoprotein or acetylcholinesterase may also be helpful in determining any other conditions that can lead to development of rachischisis.

Classification
Rachischisis occurs most commonly in utero during the development of the child. Rachischisis is a neural tube defect characterised by a complete or severe defect in the spine. The defect can be located anywhere from the cervical region to the sacrum, or through the entire length of the spine. Typical defects are clefts or splits that open the spine to the exterior environment. Rachischisis occurs around 3–4 weeks after conception when the posterior neuropore of the neural tube does not close completely. It is a multifactorial aetiology and is most typically accompanied by other defects. Rachischisis is often described as a severe form of spina bifida, with the spine not only being exposed to the exterior environment, but with the opening being large enough to allow the neural plate to spread out of the opening and to the surface.

Treatment
Rachischisis is a severe condition and survival rates for fetuses are extremely low. Babies that are born with the condition have high mortality rates and extreme developmental defects. Fetuses with the condition often spontaneously abort. Babies that are born with rachischisis are stillborn or die within a few hours to a few days of birth. Typically, medical termination of pregnancy is presented as an option to the mother once a diagnosis of rachischisis has been confirmed. As the condition is often accompanied by other deformities that not only need to be treated themselves, but also complicate the condition of rachischisis, it is difficult to treat fetuses affected </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 Vitreous membrane 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 Hypochondroplasia and can you explain it in depth? [/INST] Hypochondroplasia (HCH) is a developmental disorder caused by an autosomal dominant genetic defect in the fibroblast growth factor receptor 3 gene (FGFR3) that results in a disproportionately short stature, micromelia and a head that appears large in comparison with the underdeveloped portions of the body. It is classified as short-limbed dwarfism.

Signs and symptoms
Individuals affected by this disorder appear normal at birth. As the infant grows, however, their arms and legs do not develop properly, and their body becomes thicker and shorter than normal. The following are characteristics consistent with this condition:
Brachydactyly
Short stature
Micromelia
Skeletal dysplasia
Abnormality of femur

Cause
Hypochondroplasia is transmitted as an autosomal dominant trait affecting the FGFR3 gene on chromosome 4p16.3. There is currently no cure for this condition.

Pathophysiology
This disorder results from mutations in the proximal tyrosine kinase domain of the FGFR3 gene. This gene plays an important role in embryonic development, playing a part in regulating activities such as cell division, migration and differentiation.Hypochondroplasia can result from p. Lys650Asn as well. In FGFR3, some 20 different mutations have been associated to hypochondroplasia, and it seems to have a role in skeletal dysplasia.

Diagnosis
The diagnosis of this condition can be done via X-rays (with lack of normal distance L1 to L5), and additionally genetic testing is available to ascertain hypochondroplasia. However, the physical characteristics are one of the most important in determining the condition.

Treatment
Treatment of hypochondroplasia usually takes the form of orthopedic surgery and physical therapy. Genetic counseling is advised for individuals and their families. Specifically in the case of spinal stenosis, one option is laminectomy.

Prognosis
Life expectancy for individuals with hypochondroplasia is normal;  height is about 132–147 centimetres (4 ft 4 in – 4 ft 10 in).

See also
Achondroplasia
List of congenital disorders

References
Further reading
ed, Sally Radovick; MacGillivray, Margaret H </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 Myofascial pain syndrome and can you explain it in depth? [/INST] Myofascial pain syndrome (MPS), also known as chronic myofascial pain (CMP), is a syndrome characterized by chronic pain in multiple myofascial trigger points ("knots") and fascial (connective tissue) constrictions. It can appear in any body part. Symptoms of a myofascial trigger points include: focal point tenderness, reproduction of pain upon trigger point palpation, hardening of the muscle upon trigger point palpation, pseudo-weakness of the involved muscle, referred pain, and limited range of motion following approximately 5 seconds of sustained trigger point pressure.The cause is believed to be muscle tension or spasms within the affected musculature. Diagnosis is based on the symptoms and possible sleep studies.Treatment may include pain medication, physical therapy, mouth guards, and occasionally benzodiazepine. It is a relatively common cause of temporomandibular pain.

Signs and symptoms
Myofascial pain is pain in muscles or fascia (a type of connective tissue that surrounds muscles).  It can occur in distinct, isolated areas of the body.  Because any muscle or fascia in the body may be affected, this may cause a variety of localized symptoms.Generally speaking, the muscular pain is steady, aching, and deep. Depending on the case and location the intensity can range from mild discomfort to excruciating and "lightning-like". Knots may be visible or felt beneath the skin. The pain does not resolve on its own, even after typical first-aid self-care such as ice, heat, and rest. Myofascial pain syndromes are characterized by localized pain in an area of repetitive use or trauma with resultant trigger points that cause non-dermatomal pain radiation upon palpation.  Autonomic dysfunction and spontaneous EMG activity can be seen in the affected region.

Causes
The causes of MPS are not fully documented or understood. At least one study rules out trigger points: "The theory of myofascial pain syndrome (MPS) caused by trigger points (TrPs) .. </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 Hennekam 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 Neurodevelopmental disorder and can you explain it in depth? [/INST] Neurodevelopmental disorders are a group of disorders that affect the development of the nervous system, leading to abnormal brain function which may affect emotion, learning ability, self-control, and memory. The effects of neurodevelopmental disorders tend to last for a persons lifetime.

Types
Neurodevelopmental disorders are impairments of the growth and development of the brain and/or central nervous system. A narrower use of the term refers to a disorder of brain function that affects emotion, learning ability, self-control and memory which unfolds as an individual develops and grows.According to the DSM-5, the neurodevelopmental disorders include the following:
Attention deficit hyperactivity disorder (ADHD)
DLD - Developmental language disorder (formerly known as SLI- Specific Language Impairment)
Communication, speech, or language disorders, expressive language disorder, fluency disorder, social (pragmatic) communication disorder, and speech sound disorder.
Autism spectrum disorder (ASD)
Intellectual disabilities (IDs) or intellectual development disorder (IDD, previously called mental retardation) and global developmental delay (GDD)
Motor disorders including developmental coordination disorder, stereotypic movement disorder, and tic disorders (such as Tourettes syndrome), and CAS - Apraxia of speech
Neurogenetic disorders, such as Fragile X syndrome, Down syndrome, Rett syndrome, hypogonadotropic hypogonadal syndromes
Specific learning disorders, like dyslexia or dyscalculia.
Traumatic brain injury (including congenital injuries such as those that cause cerebral palsy) and disorders due to neurotoxicants including Minamata disease caused by mercury, behavioral disorders including conduct disorder etc. caused by other heavy metals, such as lead, chromium, platinum etc., hydrocarbons like dioxin, PBDEs and PCBs, medications and illegal drugs, like cocaine, radioactive metals like Po210(which is found in cigarettes), and others.
Fetal Alcohol Spectrum Disorders (FASD) can exhibit a combination of the above, most commonly ADHD, because of this, FASD is usually under-diagnosed, yet it is estimated that about 1 in 20 people may be affected.

Currently being researched
There are neurodevelopmental research projects examining potential new classifications of disorders including:

Nonverbal learning disorder (NLD or NVLD), a neurodevelopmental disorder thought to be linked to white matter in the right hemisphere of the brain and generally considered to include (a) low visuospatial intelligence; (b) discrepancy between verbal and visuospatial intelligence; (c) visuoconstructive and fine-motor coordination skills; (d) visuospatial memory tasks; (e) reading better than mathematical achievement; and (f) socioemotional skills.  While Nonverbal learning disorder is not categorized in the ICD or DSM as an discrete classification, "the majority of researchers and clinicians agree that the profile of NLD clearly exists (but see Spreen, 2011, for an exception), but they disagree on the need for a specific clinical category and on the criteria for its identification."

Presentation
Consequences
The multitude of neurodevelopmental disorders span a wide range of associated symptoms and severity, resulting in different degrees of mental, emotional, physical, and economic consequences for individuals, and in turn families, social groups, and society.

Causes
The development of the nervous system is tightly regulated and timed; it is influenced by both genetic programs and the environment. Any significant deviation from the normal developmental trajectory early in life can result in missing or abnormal neuronal architecture or connectivity. Because of the temporal and spatial complexity of the developmental trajectory, there are many potential causes of neurodevelopmental disorders that may affect different areas of the nervous system at different times and ages. These range from social deprivation, genetic and metabolic diseases, immune disorders, infectious diseases, nutritional factors, physical trauma, and toxic and environmental factors. Some neurodevelopmental disorders, such as autism and other pervasive developmental disorders, are considered multifactorial syndromes which have many causes that converge to a more specific neurodevelopmental manifestation.

Social deprivation
Deprivation from social and emotional care causes severe delays in brain and cognitive development. Studies with children growing up in Romanian orphanages during Nicolae Ceauşescus regime reveal profound effects of social deprivation and language deprivation on the developing brain. These effects are time-dependent. The longer children stayed in negligent institutional care, the greater the consequences. By contrast, adoption at an early age mitigated some of the effects of earlier institutionalization (abnormal psychology).

Genetic disorders
A prominent example of a genetically determined neurodevelopmental disorder is Trisomy 21, also known as Down syndrome. This disorder usually results from an extra chromosome 21, although in uncommon instances it is related to other chromosomal abnormalities such as translocation of the genetic material. It is characterized by short stature, epicanthal (eyelid) folds, abnormal fingerprints, and palm prints, heart defects, poor muscle tone (delay of neurological development), and intellectual disabilities (delay of intellectual development).Less commonly known genetically determined neurodevelopmental disorders include Fragile X syndrome. Fragile X syndrome was first described in 1943 by Martin and Bell, studying persons with family history of sex-linked "mental defects".  Rett syndrome, another X-linked disorder, produces severe functional limitations. Williams syndrome is caused by small deletions of genetic material from chromosome 7.
The most common recurrent Copy Number Variant disorder is 22q11.2 deletion syndrome (formerly DiGeorge or velocardiofacial syndrome), followed by Prader-Willi syndrome and Angelman syndrome.

Immune dysfunction
Immune reactions during pregnancy, both maternal and of the developing child, may produce neurodevelopmental disorders. One typical immune reaction in infants and children is PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection. Another disorder is Sydenhams chorea, which results in more abnormal movements of the body and fewer psychological sequellae. Both are immune reactions against brain tissue that follow infection by Streptococcus bacteria. Susceptibility to these immune diseases may be genetically determined, so sometimes several family members may have one or both of them following an epidemic of Strep infection.

Infectious diseases
Systemic infections can result in neurodevelopmental consequences, when they occur in infancy and childhood of humans, but would not be called a primary neurodevelopmental disorder. For example HIV Infections of the head and brain, like brain abscesses, meningitis or encephalitis have a high risk of causing neurodevelopmental problems and eventually a disorder. For example, measles can progress to subacute sclerosing panencephalitis.
A number of infectious diseases can be transmitted congenitally (either before or at birth), and can cause serious neurodevelopmental problems, as for example the viruses HSV, CMV, rubella (congenital rubella syndrome), Zika virus, or bacteria like Treponema pallidum in congenital syphilis, which may progress to neurosyphilis if it remains untreated. Protozoa like Plasmodium or Toxoplasma which can cause congenital toxoplasmosis with multiple cysts in the brain and other organs, leading to a variety of neurological deficits.
Some cases of schizophrenia may be related to congenital infections, though the majority are of unknown causes.

Metabolic disorders
Metabolic disorders in either the mother or the child can cause neurodevelopmental disorders. Two examples are diabetes mellitus (a multifactorial disorder) and phenylketonuria (an inborn error of metabolism). Many such inherited diseases may directly affect the childs metabolism and neural development but less commonly they can indirectly affect the child during gestation. (See also teratology).
In a child, type 1 diabetes can produce neurodevelopmental damage by the effects of excess or insufficient glucose. The problems continue and may worsen throughout childhood if the diabetes is not well controlled. Type 2 diabetes may be preceded in its onset by impaired cognitive functioning.A non-diabetic fetus can also be subjected to glucose effects if its mother has undetected gestational diabetes. Maternal diabetes causes excessive birth size, making it harder for the infant to pass through the birth canal without injury or it can directly produce early neurodevelopmental deficits. Usually the neurodevelopmental symptoms will decrease in later childhood.Phenylketonuria, also known as PKU, can induce neurodevelopmental problems and children with PKU require a strict diet to prevent intellectual disability and other disorders. In the maternal form of PKU, excessive maternal phenylalanine can be absorbed by the fetus even if the fetus has not inherited the disease. This can produce intellectual disability and other disorders.

Nutrition
Nutrition disorders and nutritional deficits may cause neurodevelopmental disorders, such as spina bifida, and the rarely occurring anencephaly, both of which are neural tube defects with malformation and dysfunction of the nervous system and its supporting structures, leading to serious physical disability and emotional sequelae. The most common nutritional cause of neural tube defects is folic acid deficiency in the mother, a B vitamin usually found in fruits, vegetables, whole grains, and milk products </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 Hematosalpinx 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 Lobar pneumonia and can you explain it in depth? [/INST] Lobar pneumonia is a form of pneumonia characterized by inflammatory exudate within the intra-alveolar space resulting in consolidation that affects a large and continuous area of the lobe of a lung.It is one of three anatomic classifications of pneumonia (the other being bronchopneumonia and atypical pneumonia). In children round pneumonia develops instead because the  pores of Kohn which allow the lobar spread of infection are underdeveloped.

Mechanism
The invading organism starts multiplying, thereby releasing toxins that cause inflammation and edema of the lung parenchyma. This leads to the accumulation of cellular debris within the lungs. This leads to consolidation or solidification, which is a term that is used for macroscopic or radiologic appearance of the lungs affected by pneumonia.
Bacterial pneumonia is mainly classified into lobar and diffuse depending on the degree of lung irritation or damage.

Stages
Lobar pneumonia usually has an acute progression.
Classically, the disease has four stages:
Congestion in the first 24 hours: This stage is characterized histologically by vascular engorgement, intra-alveolar fluid, small numbers of neutrophils, often numerous bacteria. Grossly, the lung is heavy and hyperemic.
Red hepatization or consolidation: Vascular congestion persists, with extravasation of red blood cells into alveolar spaces, along with increased numbers of neutrophils and fibrin. The filling of airspaces by the exudate leads to a gross appearance of solidification, or consolidation, of the alveolar parenchyma. This appearance has been likened to that of the liver, hence the term "hepatization".
Grey hepatization: Red blood cells disintegrate, with persistence of the neutrophils and fibrin. The alveoli still appear consolidated, but grossly the color is paler and the cut surface is drier. This is when death typically occurs in severe cases.
Resolution (complete recovery): The exudate is digested by enzymatic activity, and cleared by macrophages or by cough mechanism </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 Benzodiazepine withdrawal syndrome and can you explain it in depth? [/INST] Benzodiazepine withdrawal syndrome—often abbreviated to benzo withdrawal or BZD withdrawal —is the cluster of signs and symptoms that emerge when a person who has been taking benzodiazepines, either medically or recreationally, and has developed a physical dependence, undergoes dosage reduction or discontinuation.
Development of physical dependence and the resulting withdrawal symptoms, some of which may last for years, may result from taking the medication as prescribed. Benzodiazepine withdrawal is characterized by sleep disturbance, irritability, mast cell activation, increased tension and anxiety, panic attacks, hand tremor, shaking, sweating, difficulty with concentration, confusion and cognitive difficulty, memory problems, dry retching and nausea, weight loss, palpitations, headache, muscular pain and stiffness, a host of perceptual changes, hallucinations, seizures, psychosis, and increased risk of suicide (see "signs and symptoms" section below for full list).  Further, these symptoms are notable for the manner in which they wax and wane and vary in severity from day to day or week by week instead of steadily decreasing in a straightforward monotonic manner. This phenomenon is often referred to as "waves" and "windows".
It is a potentially serious condition, and is complex and often protracted in its course. Long-term benzodiazepine use, defined as daily use for at least three months, is not desirable because of the associated increased risk of dependence, dose escalation, loss of efficacy, increased risk of accidents and falls, particularly for the elderly, as well as cognitive, neurological, and intellectual impairments. Use of short-acting hypnotics, while being effective at initiating sleep, worsens the second half of sleep due to withdrawal effects.Benzodiazepine withdrawal can be severe and provoke life-threatening withdrawal symptoms, such as seizures, particularly with abrupt or overly rapid dosage reduction from high doses or long-time use. A severe withdrawal response can nevertheless occur despite gradual dose reduction, or from relatively low doses in short-time users; even after a single large dose in animal models. A minority of individuals will experience a protracted withdrawal syndrome, whose symptoms may persist at a sub-acute level for months or years after cessation of benzodiazepines. The likelihood of developing a protracted withdrawal syndrome can be minimized by a slow, gradual reduction in dosage.Chronic exposure to benzodiazepines causes neural adaptations that counteract the drugs effects, leading to tolerance and dependence. Despite taking a constant therapeutic dose, long-term use of benzodiazepines may lead to the emergence of withdrawal-like symptoms, particularly between doses, when patients are treated with shorter-acting benzodiazepines. When the drug is discontinued or the dosage reduced, withdrawal symptoms may appear and remain until the body has reversed the long-term physiological adaptations. These rebound symptoms may be identical to the symptoms for which the drug was initially taken, or may be part of discontinuation symptoms. In severe cases, the withdrawal reaction may exacerbate or resemble serious psychiatric and medical conditions, such as mania, schizophrenia, and, especially at high doses, seizure disorders. Failure to recognize discontinuation symptoms can lead to false evidence for the need to take benzodiazepines, which in turn leads to withdrawal failure and reinstatement of benzodiazepines, often at higher doses.Awareness of the withdrawal reactions, individualized taper strategies according to withdrawal severity, the addition of alternative strategies such as reassurance and referral to benzodiazepine withdrawal support groups, all increase the success rate of withdrawal.

Signs and symptoms
Withdrawal effects caused by sedative-hypnotics discontinuation, such as benzodiazepines, barbiturates, or alcohol, can cause serious medical complications. They are cited to be more hazardous to withdraw from than opioids. Users typically receive little advice and support for discontinuation. Some withdrawal symptoms are identical to the symptoms for which the medication was originally prescribed, and can be acute or protracted in duration. Onset of symptoms from long half-life benzodiazepines might be delayed for up to three weeks, although withdrawal symptoms from short-acting ones often present early, usually within 24–48 hours. There may be no fundamental differences in symptoms from either high or low dose discontinuation, but symptoms tend to be more severe from higher doses.Daytime reemergence and rebound withdrawal symptoms, sometimes confused with interdose withdrawal, may occur once dependence has set in. Reemergence is the return of symptoms for which the drug was initially prescribed, in contrast, rebound symptoms are a return of the symptoms for which the benzodiazepine was initially taken, but at a more intense level than before; whereas interdose withdrawal is when a prior dosage of drug wears off and beginnings of an entirely new cycle of withdrawal sets in, the symptoms of which dissipate upon taking the next dosage but after which yet another entirely new cycle of withdrawal begins when that dosage wears off, a new onset of withdrawal between each dosage thus called interdose withdrawal and if not properly treated can recur indefinitely in a vicious circle (for which a benzo with a long half life, e.g. diazepam, can be substituted so the drug does not wear off between doses).Withdrawal symptoms may appear for the first time during dose reduction, and include insomnia, anxiety, distress, weight loss, dizziness, night sweats, shakes, muscle twitches, aphasia, panic attacks, depression, derealization, paranoia, indigestion, diarrhea, photophobia etc., and are more commonly associated with short-acting benzodiazepines discontinuation, like triazolam. Daytime symptoms can occur after a few days to a few weeks of administration of nightly benzodiazepines or z-drugs such as zopiclone; withdrawal-related insomnia rebounds worse than baseline,  and for rapidly eliminated benzodiazepines, including triazolam and temazepam, this may occur even when used briefly and intermittently, according to a small 1991 study (n=18).The following symptoms may emerge during gradual or abrupt dosage reduction:

Rapid discontinuation may result in a more serious syndrome

As withdrawal progresses, patients often find their physical and mental health improves with improved mood and improved cognition.

Mechanism
The neuroadaptive processes involved in tolerance, dependence, and withdrawal mechanisms implicate both the GABAergic and the glutamatergic systems. Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the central nervous system; roughly one-quarter to one-third of synapses use GABA. GABA mediates the influx of chloride ions through ligand-gated chloride channels called GABAA receptors. When chloride enters the nerve cell, the cell membrane potential hyperpolarizes thereby inhibiting depolarization, or reduction in the firing rate of the post-synaptic nerve cell. Benzodiazepines potentiate the action of GABA, by binding a site between the α and γ subunits of the 5-subunit receptor thereby increasing the frequency of the GABA-gated chloride channel opening in the presence of GABA.When potentiation is sustained by long-term use, neuroadaptations occur which result in decreased GABAergic response. What is certain is that surface GABAA receptor protein levels are altered in response to benzodiazepine exposure, as is receptor turnover rate. The exact reason for the reduced responsiveness has not been elucidated but down-regulation of the number of receptors has only been observed at some receptor locations including in the pars reticulata of the substantia nigra; down-regulation of the number of receptors or internalization does not appear to be the main mechanism at other locations. Evidence exists for other hypotheses including changes in the receptor conformation, changes in turnover, recycling, or production rates, degree of phosphorylation and receptor gene expression, subunit composition, decreased coupling mechanisms between the GABA and benzodiazepine site, decrease in GABA production, and compensatory increased glutamatergic activity. A unified model hypothesis involves a combination of internalization of the receptor, followed by preferential degradation of certain receptor sub-units, which provides the nuclear activation for changes in receptor gene transcription.It has been postulated that when benzodiazepines are cleared from the brain, these neuroadaptations are "unmasked", leading to unopposed excitability of the neuron. Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. Increased glutamate excitatory activity during withdrawal may lead to sensitization or kindling of the CNS, possibly leading to worsening cognition and symptomatology and making each subsequent withdrawal period worse. Those who have a prior history of withdrawing from benzodiazepines are found to be less likely to succeed the next time around.

Diagnosis
In severe cases, the withdrawal reaction or protracted withdrawal may exacerbate or resemble serious psychiatric and medical conditions, such as mania, schizophrenia, agitated depression, panic disorder, generalised anxiety disorder, and complex partial seizures and, especially at high doses, seizure disorders. Failure to recognize discontinuation symptoms can lead to false evidence for the need to take benzodiazepines, which in turn leads to withdrawal failure and reinstatement of benzodiazepines, often to higher doses. Pre-existing disorder or other causes typically do not improve, whereas symptoms of protracted withdrawal gradually improve over the ensuing months.Symptoms may lack a psychological cause and can fluctuate in intensity with periods of good and bad days until eventual recovery.

Prevention
According to the British National Formulary, it is better to withdraw too slowly rather than too quickly from benzodiazepines. The rate of dosage reduction is best carried out so as to minimize the symptoms intensity and severity. Anecdotally, a slow rate of reduction may reduce the risk of developing a severe protracted syndrome.
Long half-life benzodiazepines like diazepam or chlordiazepoxide are preferred to minimize rebound effects and are available in low dose forms. Some people may not fully stabilize between dose reductions, even when the rate of reduction is slowed. Such people sometimes simply need to persist as they may not feel better until they have been fully withdrawn from them for a period of time.

Management
Management of benzodiazepine dependence involves considering the persons age, comorbidity and the pharmacological pathways of benzodiazepines. Psychological interventions may provide a small but significant additional benefit over gradual dose reduction alone at post-cessation and at follow-up. The psychological interventions studied were relaxation training, cognitive-behavioral treatment of insomnia, and self-monitoring of consumption and symptoms, goal-setting, management of withdrawal and coping with anxiety.There is no standard approach to managing benzodiazepine withdrawal.
With sufficient motivation and the proper approach, almost anyone can successfully withdraw from benzodiazepines. However, a prolonged and severe withdrawal syndrome can cause profound disability, which may lead to breakdown of relationships, loss of employment, financial difficulties, as well as more serious adverse effects such as hospitalization and suicide. As such, long-term users should not be forced to discontinue against their will.Over-rapid withdrawal, lack of explanation, and failure to reassure individuals that they are experiencing temporary withdrawal symptoms led some people to experience increased panic and fears they are going mad, with some people developing a condition similar to post-traumatic stress disorder as a result.  A slow withdrawal regimen, coupled with reassurance from family, friends, and peers improves the outcome. According to a 2015 Cochrane review, cognitive behavior therapy plus taper was effective in achieving discontinuation in the short-term but the effect was not certain after six months.

Medications
While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use. Some studies found that the abrupt substitution of substitutive pharmacotherapy was actually less effective than gradual dose reduction alone, and only three studies found benefits of adding melatonin, paroxetine, trazodone, or valproate in conjunction with a gradual dose reduction.
Antipsychotics are generally ineffective for benzodiazepine withdrawal-related psychosis. Antipsychotics should be avoided during benzodiazepine withdrawal as they tend to aggravate withdrawal symptoms, including convulsions. Some antipsychotic agents may be riskier than others during withdrawal, especially clozapine, olanzapine or low potency phenothiazines (e.g., chlorpromazine), as they lower the seizure threshold and can worsen withdrawal effects; if used, extreme caution is required.
Barbiturates are cross tolerant to benzodiazepines and should generally be avoided; however phenobarbital can be used, as it is relatively safe, see below.
Benzodiazepines or cross tolerant drugs should be avoided after discontinuation, even occasionally. These include the nonbenzodiazepines Z-drugs, which have a similar mechanism of action. This is because tolerance to benzodiazepines has been demonstrated to be still present at four months to two years after withdrawal depending on personal biochemistry. Re-exposures to benzodiazepines typically resulted in a reactivation of the tolerance and benzodiazepine withdrawal syndrome.
Bupropion, which is used primarily as an antidepressant and smoking cessation aid, is contraindicated in persons experiencing abrupt withdrawal from benzodiazepines or other sedative-hypnotics (e.g. alcohol), due to an increased risk of seizures.
Buspirone augmentation was not found to increase the discontinuation success rate.
Caffeine may worsen withdrawal symptoms because of its stimulatory properties. At least one animal study has shown some modulation of the benzodiazepine site by caffeine, which produces a lowering of seizure threshold.
Carbamazepine, an anticonvulsant, appears to have some beneficial effects in the treatment and management of benzodiazepine withdrawal; however, research is limited and thus the ability of experts to make recommendations on its use for benzodiazepine withdrawal is not possible at present.
Ethanol, the primary alcohol in alcoholic beverages, even mild to moderate use, has been found to be a significant predictor of withdrawal failure, probably because of its cross tolerance with benzodiazepines.
Flumazenil has been found to stimulate the reversal of tolerance and the normalization of receptor function. However, further research is needed in the form of randomised trials to demonstrate its role in the treatment of benzodiazepine withdrawal. Flumazenil stimulates the up-regulation and reverses the uncoupling of benzodiazepine receptors to the GABAA receptor, thereby reversing tolerance and reducing withdrawal symptoms and relapse rates. Because of limited research and experience compared to the possible risks involved, the flumazenil detoxification method is controversial and can only be done as an inpatient procedure under medical supervision.Flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.A study into the effects of the benzodiazepine receptor antagonist, flumazenil, on benzodiazepine withdrawal symptoms persisting after withdrawal was carried out by Lader and Morton. Study subjects had been benzodiazepine-free for between one month and five years, but all reported persisting withdrawal effects to varying degrees. Persistent symptoms included clouded thinking, tiredness, muscular symptoms such as neck tension, depersonalisation, cramps and shaking and the characteristic perceptual symptoms of benzodiazepine withdrawal, namely, pins and needles feeling, burning skin, pain and subjective sensations of bodily distortion. Therapy with 0.2–2 mg of flumazenil intravenously was found to decrease these symptoms in a placebo-controlled study. This is of interest as benzodiazepine receptor antagonists are neutral and have no clinical effects. The author of the study suggested the most likely explanation is past benzodiazepine use and subsequent tolerance had locked the conformation of the GABA-BZD receptor complex into an inverse agonist conformation, and the antagonist flumazenil resets benzodiazepine receptors to their original sensitivity. Flumazenil was found in this study to be a successful treatment for protracted benzodiazepine withdrawal syndrome, but further research is required. A study by Professor Borg in Sweden produced similar results in patients in protracted withdrawal. In 2007, Hoffmann–La Roche the makers of flumazenil, acknowledged the existence of protracted benzodiazepine withdrawal syndromes, but did not recommended flumazenil to treat the condition.Fluoroquinolone antibiotics have been noted to increase the incidence of a CNS toxicity from 1% in the general population, to 4% in benzodiazepine-dependent population or in those undergoing withdrawal from them. This is probably the result of their GABA antagonistic effects as they have been found to competitively displace benzodiazepines from benzodiazepine receptor sites. This antagonism can precipitate acute withdrawal symptoms, that can persist for weeks or months before subsiding.  The symptoms include depression, anxiety, psychosis, paranoia, severe insomnia, paresthesia, tinnitus, hypersensitivity to light and sound, tremors, status epilepticus, suicidal thoughts and suicide attempt. Fluoroquinolone antibiotics should be contraindicated in patients who are dependent on or in benzodiazepine withdrawal. NSAIDs have some mild GABA antagonistic properties and animal research indicate that some may even displace benzodiazepines from their binding site. However, NSAIDs taken in combination with fluoroquinolones cause a very significant increase in GABA antagonism, GABA toxicity, seizures, and other severe adverse effects.
Imidazenil has received some research for management of benzodiazepine withdrawal, but is not currently used in withdrawal.
Imipramine was found to statistically increase the discontinuation success rate.
Melatonin augmentation was found to statistically increase the discontinuation success rate for people with insomnia.
Phenobarbital, (a barbiturate), is used at "detox" or other inpatient facilities to prevent seizures during rapid withdrawal or cold turkey. The phenobarbital is followed by a one- to two-week taper, although a slow taper from phenobarbital is preferred. In a comparison study, a rapid taper using benzodiazepines was found to be superior to a phenobarbital rapid taper.
Pregabalin may help reduce the severity of benzodiazepine withdrawal symptoms, and reduce the risk of relapse.
Propranolol was not found to increase the discontinuation success rate.
SSRI antidepressants have been found to have little value in the treatment of benzodiazepine withdrawal.
Trazodone was not found to increase the discontinuation success rate.

Inpatient treatment
Inpatient drug detox or rehabilitation facilities may be inappropriate for those who have become tolerant or dependent while taking the drug as prescribed, as opposed to recreational use. Such inpatient referrals may be traumatic for these individuals.

Prognosis
A 2006 meta-analysis found evidence for the efficacy of stepped care: minimal intervention (e.g. send an advisory letter, or meet a large number of patients to advise discontinuation), followed by systematic tapered discontinuation alone without augmentation if the first try was unsuccessful. Cognitive behavioral therapy improved discontinuation success rates for panic disorder, melatonin for insomnia, and flumazenil or sodium valproate for general long-term benzodiazepine use. A ten-year follow-up found that more than half of those who had successfully withdrawn from long-term use were still abstinent two years later and that if they were able to maintain this state at two years, they were likely to maintain this state at the ten-year follow-up. One study found that after one year of abstinence from long-term use of benzodiazepines, cognitive, neurological and intellectual impairments had returned to normal.Those who had a prior psychiatric diagnosis had a similar success rate from a gradual taper at a two-year follow-up. Withdrawal from benzodiazepines did not lead to an increased use of antidepressants.

Withdrawal process
It can be too difficult to withdraw from short- or intermediate-acting benzodiazepines because of the intensity of the rebound symptoms felt between doses. Moreover, short-acting benzodiazepines appear to produce a more intense withdrawal syndrome. For this reason, discontinuation is sometimes carried out by first substituting an equivalent dose of a short-acting benzodiazepine with a longer-acting one like diazepam or chlordiazepoxide. Failure to use the correct equivalent amount can precipitate a severe withdrawal reaction. Benzodiazepines with a half-life of more than 24 hours include chlordiazepoxide, diazepam, clobazam, clonazepam, chlorazepinic acid, ketazolam, medazepam, nordazepam, and prazepam.  Benzodiazepines with a half-life of less than 24 hours include alprazolam, bromazepam, brotizolam, flunitrazepam, loprazolam, lorazepam, lormetazepam, midazolam, nitrazepam, oxazepam, and temazepam. The resultant equivalent dose is then gradually reduced.
The consensus is to reduce dosage gradually over several weeks, e.g. 4 or more weeks for diazepam doses over 30 mg/day,
with the rate determined by the persons ability to tolerate symptoms.
The recommended reduction rates range from 50% of the initial dose every week or so,
to 10-25% of the daily dose every 2 weeks.
For example, the reduction rate used in the Heather Ashton protocol calls for eliminating 10% of the remaining dose every two to four weeks, depending on the severity and response to reductions with the final dose at 0.5 mg dose of diazepam or 2.5 mg dose of chlordiazepoxide.
For most people, discontinuation over 4–6 weeks or 4–8 weeks is suitable.
A prolonged period of reduction for longer than six months should be avoided to prevent the withdrawal process from becoming a "morbid focus" for the person.

Duration
After the last dose has been taken, the acute phase of the withdrawal generally lasts for about two months although withdrawal symptoms, even from low-dose use, can persist for six to twelve months gradually improving over that period, however, clinically significant withdrawal symptoms may persist for years, although gradually declining.
A clinical trial of patients taking the benzodiazepine alprazolam for as short as eight weeks triggered protracted symptoms of memory deficits which were still present up to eight weeks after cessation of alprazolam.

Protracted withdrawal syndrome
Protracted withdrawal syndrome refers to symptoms persisting for months or even years. A significant minority of people withdrawing from benzodiazepines, perhaps 10% to 15%, experience a protracted withdrawal syndrome which can sometimes be severe. Symptoms may include tinnitus, psychosis, cognitive deficits, gastrointestinal complaints, insomnia, paraesthesia (tingling and numbness), pain (usually in limbs and extremities), muscle pain, weakness, tension, painful tremor, shaking attacks, jerks, dizziness and blepharospasm and may occur even without a pre-existing history of these symptoms.  Tinnitus occurring during dose reduction or discontinuation of benzodiazepines is alleviated by recommencement of benzodiazepines. Dizziness is often reported as being the withdrawal symptom that lasts the longest.
A study testing neuropsychological factors found psychophysiological markers differing from normals, and concluded that protracted withdrawal syndrome was a genuine iatrogenic condition caused by the long-term use. The causes of persisting symptoms are a combination of pharmacological factors such as persisting drug induced receptor changes, psychological factors both caused by the drug and separate from the drug and possibly in some cases, particularly high dose users, structural brain damage or structural neuronal damage. Symptoms continue to improve over time, often to the point where people eventually resume their normal lives, even after years of incapacity.A slow withdrawal rate significantly reduces the risk of a protracted or severe withdrawal state. Protracted withdrawal symptoms can be punctuated by periods of good days and bad days. When symptoms increase periodically during protracted withdrawal, physiological changes may be present, including dilated pupils as well as an increase in blood pressure and heart rate. The change in symptoms has been proposed to be due to changes in receptor sensitivity for GABA during the process of tolerance reversal. A meta-analysis found cognitive impairments in many areas due to benzodiazepine use show improvements after six months of withdrawal, but significant impairments in most areas may be permanent or may require more than six months to reverse.Protracted symptoms continue to fade over a period of many months or several years. There is no known cure for protracted benzodiazepine withdrawal syndrome except time, however, the medication flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.

Epidemiology
The severity and length of the withdrawal syndrome is likely determined by various factors, including rate of tapering, length of use and dosage size, and possible genetic factors. Those who have a prior history of withdrawing from benzodiazepines may have a sensitized or kindled central nervous system leading to worsening cognition and symptomatology, and making each subsequent withdrawal period worse.

Special populations
Pediatrics
A neonatal withdrawal syndrome, sometimes severe, can occur when the mother had taken benzodiazepines, especially during the third trimester.  Symptoms include hypotonia, apnoeic spells, cyanosis, impaired metabolic responses to cold stress, and seizures. The neonatal benzodiazepine withdrawal syndrome has been reported to persist from hours to months after birth.A withdrawal syndrome is seen in about 20% of pediatric intensive care unit children after infusions with benzodiazepines or opioids. The likelihood of having the syndrome correlates with total infusion duration and dose, although duration is thought to be more important. Treatment for withdrawal usually involves weaning over a 3- to 21-day period if the infusion lasted for more than a week. Symptoms include tremors, agitation, sleeplessness, inconsolable crying, diarrhea and sweating. In total, over fifty withdrawal symptoms are listed in this review article. Environmental measures aimed at easing the symptoms of neonates with severe abstinence syndrome had little impact, but providing a quiet sleep environment helped in mild cases.

Pregnancy
Discontinuing benzodiazepines or antidepressants abruptly due to concerns of teratogenic effects of the medications has a high risk of causing serious complications, so is not recommended. For example, abrupt withdrawal of benzodiazepines or antidepressants has a high risk of causing extreme withdrawal symptoms, including suicidal ideation and a severe rebound effect of the return of the underlying disorder if present. This can lead to hospitalisation and potentially, suicide. One study reported one-third of mothers who suddenly discontinued or very rapidly tapered their medications became acutely suicidal due to unbearable symptoms. One woman had a medical abortion, as she felt she could no longer cope, and another woman used alcohol in a bid to combat the withdrawal symptoms from benzodiazepines. Spontaneous abortions may also result from abrupt withdrawal of psychotropic medications, including benzodiazepines. The study reported physicians generally are not aware of the severe consequences of abrupt withdrawal of psychotropic medications such as benzodiazepines or antidepressants.

Elderly
A study of the elderly who were benzodiazepine dependent found withdrawal could be carried out with few complications and could lead to improvements in sleep and cognitive abilities. At 52 weeks after successful withdrawal, a 22% improvement in cognitive status was found, as well as improved social functioning. Those who remained on benzodiazepines experienced a 5% decline in cognitive abilities, which seemed to be faster than that seen in normal aging, suggesting the longer the intake of benzodiazepines, the worse the cognitive effects become. Some worsening of symptoms were seen in the first few months of benzodiazepine abstinence, but at a 24-week follow-up, elderly subjects were clearly improved compared to those who remained on benzodiazepines. Improvements in sleep were seen at the 24- and 52-week follow-ups. The authors concluded benzodiazepines were not effective in the long term for sleep problems except in suppressing withdrawal-related rebound insomnia. Improvements were seen between 24 and 52 weeks after withdrawal in many factors, including improved sleep and several cognitive and performance abilities. Some cognitive abilities, which are sensitive to benzodiazepines, as well as age, such as episodic memory, did not improve </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 inflammatory demyelinating polyneuropathy and can you explain it in depth? [/INST] Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy (because it involves the nerve roots). CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. It is one of several types of neuropathy.

Types
Several variants have been reported. Specially important are:

An asymmetrical variant of CIDP is known as Lewis-Sumner Syndrome. or MADSAM (multifocal acquired demyelinating sensory and motor neuropathy)
A variant with CNS involvement named combined central and peripheral demyelination (CCPD)Currently there is one special variant in which the CNS is also affected. It is termed "combined central and peripheral demyelination" (CCPD) and is special because it belongs at the same time to the CDIP syndrome and to the multiple sclerosis spectrum. These cases seem to be related to the presence of anti-neurofascin autoantibodies.

Causes
Chronic inflammatory demyelinating polyneuropathy (or polyradiculoneuropathy) is considered an autoimmune disorder destroying myelin, the protective covering of the nerves. Typical early symptoms are "tingling" (sort of electrified vibration or paresthesia) or numbness in the extremities, frequent (night) leg cramps, loss of reflexes (in knees), muscle fasciculations, "vibration" feelings, loss of balance, general muscle cramping and nerve pain.  CIDP is extremely rare but under-recognized and under-treated due to its heterogeneous presentation (both clinical and electrophysiological) and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is favoured in preventing irreversible axonal loss and improving functional recovery.There is a lack of awareness and treatment of CIDP.  Although there are stringent research criteria for selecting patients for clinical trials, there are no generally agreed-upon clinical diagnostic criteria for CIDP due to its different presentations in symptoms and objective data. Application of the present research criteria to routine clinical practice often misses the diagnosis in a majority of patients, and patients are often left untreated despite progression of their disease.CIDP has been associated with diabetes mellitus, HIV infection, and paraproteinemias.

Variants with paranodal autoantibodies
Some variants of CIDP present autoimmunity against proteins of the node of Ranvier. These variants comprise a subgroup of inflammatory neuropathies with IgG4 autoantibodies against the paranodal proteins neurofascin-155, contactin-1 and caspr-1.These cases are special not only because of their pathology, but also because they are non-responsive to the standard treatment. They are responsive to Rituximab instead.Also some cases of combined central and peripheral demyelination (CCPD) could be produced by neurofascins.

Autoantibodies of the IgG3 Subclass in CIDP
Autoantibodies to components of the Ranvier nodes, specially autoantibodies the Contactin-associated protein 1 (CASPR), cause a form of CIDP with an acute "Guillain-Barre-like" phase, followed by a chronic phase with progressive symptoms. Different IgG subclasses are associated with the different phases of the disease. IgG3 Caspr autoantibodies were found during the acute GBS-like phase, while IgG4 Caspr autoantibodies were present during the chronic phase of disease.

Diagnosis and symptoms
Diagnosis is typically made on the basis of presenting symptoms in tandem with electrodiagnostic testing or a nerve biopsy. Doctors may use a lumbar puncture to verify the presence of increased cerebrospinal fluid protein.

Differential diagnosis
CIBP variants are among several types of immune-mediated neuropathies recognised. These include:

Chronic inflammatory demyelinating polyneuropathy (CIDP) with subtypes:
Classical CIDP
CIDP with diabetes
CIDP/monoclonal gammopathy of undetermined significance
Sensory CIDP
Multifocal motor neuropathy
Multifocal acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome)
Multifocal acquired sensory and motor neuropathy
Distal acquired demyelinating sensory neuropathy
Guillain–Barré syndrome with subtypes:
Acute inflammatory demyelinating polyradiculoneuropathy
Acute motor axonal neuropathy
Acute motor and sensory axonal neuropathy
Acute pandysautonomia
Miller Fisher syndrome
IgM monoclonal gammopathies with subtypes:
Waldenströms macroglobulinemia
Mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome
Myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS)Other possible diagnoses are

Bickerstaff brainstem encephalitis
Fisher syndrome
Guillain–Barré syndromeFor this reason a diagnosis of chronic inflammatory demyelinating polyneuropathy needs further investigations. The diagnosis is usually provisionally made through a clinical neurological examination.

Symptoms
Symptoms such as diminished or absent deep-tendon reflexes and sensory ataxia are common. Other symptoms include proximal and distal muscle weakness in the limbs.Patients usually present with a history of weakness, numbness, tingling, pain and difficulty in walking.  They may additionally present with fainting spells while standing up or burning pain in extremities. Some patients may have sudden onset of back pain or neck pain radiating down the extremities, usually diagnosed as radicular pain. These symptoms are usually progressive and may be intermittent.Autonomic system dysfunction can occur; in such a case, the patient would complain of orthostatic dizziness, problems breathing, eye, bowel, bladder  and cardiac problems. The patient may also present with a single cranial nerve or peripheral nerve dysfunction.On examination the patients may have weakness, and loss of deep tendon reflexes (rarely increased or normal). There may be atrophy (shrinkage) of muscles, fasciculations (twitching) and loss of sensation. Patients may have multi-focal motor neuropathy, as they have no sensory loss.Most experts consider the necessary duration of symptoms to be greater than 8 weeks for the diagnosis of CIDP to be made.
Fatigue has been identified as common in CIDP patients, but it is unclear how much this is due to primary (due to the disease action on the body) or secondary effects (impacts on the whole person of being ill with CIDP).

Tests
Typical diagnostic tests include:

Electrodiagnostics – electromyography (EMG) and nerve conduction study (NCS). In usual CIDP, the nerve conduction studies show demyelination. These findings include:a reduction in nerve conduction velocities;
the presence of conduction block or abnormal temporal dispersion in at least one motor nerve;
prolonged distal latencies in at least two nerves;
absent F waves or prolonged minimum F wave latencies in at least two motor nerves. (In some case EMG/NCV can be normal).
Serum test to exclude other autoimmune diseases.
Lumbar puncture and serum test for anti-ganglioside antibodies. These antibodies are present in the branch of CIDP diseases comprised by anti-GM1, anti-GD1a, and anti-GQ1b.
Sural nerve biopsy; biopsy is considered for those patients in whom the diagnosis is not completely clear, when other causes of neuropathy (e.g., hereditary, vasculitic) cannot be excluded, or when profound axonal involvement is observed on EMG.
Ultrasound of the peripheral nerves may show swelling of the affected nerves.
Magnetic resonance imaging can also be used in the diagnostic workup.In some cases electrophysiological studies fail to show any evidence of demyelination. Though conventional electrophysiological diagnostic criteria are not met, the patient may still respond to immunomodulatory treatments. In such cases, presence of clinical characteristics suggestive of CIDP are critical, justifying full investigations, including sural nerve biopsy.

Treatment
First-line treatment for CIDP is currently intravenous immunoglobulin and other treatments include corticosteroids (e.g., prednisone), and plasmapheresis (plasma exchange) which may be prescribed alone or in combination with an immunosuppressant drug. Recent controlled studies show subcutaneous immunoglobulin appears to be as effective for CIDP treatment as intravenous immunoglobulin in most patients, and with fewer systemic side effects.Intravenous immunoglobulin and plasmapheresis have proven benefit in randomized, double-blind, placebo-controlled trials. Despite less definitive published evidence of efficacy, corticosteroids are considered standard therapies because of their long history of use and cost effectiveness. Intravenous immunoglobulin is probably the first-line CIDP treatment, but is extremely expensive. For example, in the U.S., a single 65 g dose of Gamunex brand in 2010 might be billed at the rate of $8,000 just for the immunoglobulin—not including other charges such as nurse administration.Immunosuppressive drugs are often of the cytotoxic (chemotherapy) class, including rituximab (Rituxan) which targets B cells, and cyclophosphamide, a drug which reduces the function of the immune system. Ciclosporin has also been used in CIDP but with less frequency as it is a newer approach. Ciclosporin is thought to bind to immunocompetent lymphocytes, especially T-lymphocytes.Non-cytotoxic immunosuppressive treatments usually include the anti-rejection transplant drugs azathioprine (Imuran/Azoran) and mycophenolate mofetil (Cellcept). In the U.S., these drugs are used "off-label", meaning that they do not have an indication for the treatment of CIDP in their package inserts. Before azathioprine is used, the patient should first have a blood test that ensures that azathioprine can safely be used.Anti-thymocyte globulin, an immunosuppressive agent that selectively destroys T lymphocytes is being studied for use in CIDP. Anti-thymocyte globulin is the gamma globulin fraction of antiserum from animals that have been immunized against human thymocytes. It is a polyclonal antibody. Although chemotherapeutic and immunosuppressive agents have shown to be effective in treating CIDP, significant evidence is lacking, mostly due to the heterogeneous nature of the disease in the patient population in addition to the lack of controlled trials.A review of several treatments found that azathioprine, interferon alpha and methotrexate were not effective. Cyclophosphamide and rituximab seem to have some response. Mycophenolate mofetil may be of use in milder cases. Immunoglobulin and steroids are the first line choices for treatment.In severe cases of CIDP, when second-line immunomodulatory drugs are not efficient, autologous hematopoietic stem cell transplantation is sometimes performed. The treatment may induce long-term remission even in severe treatment-refractory cases of CIDP. To improve outcome, it has been suggested that it should be initiated before irreversible axonal damage has occurred. However, a precise estimation of its clinical efficacy for CIDP is not available, as randomized controlled trials have not been performed.Physical therapy and occupational therapy may improve muscle strength, activities of daily living, mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.

Prognosis
As in multiple sclerosis, another demyelinating condition, it is not possible to predict with certainty how CIDP will affect patients over time. The pattern of relapses and remissions varies greatly with each patient. A period of relapse can be very disturbing, but many patients make significant recoveries.If diagnosed early, initiation of early treatment to prevent loss of nerve axons is recommended. However, many individuals are left with residual numbness, weakness, tremors, fatigue and other symptoms which can lead to long-term morbidity and diminished quality of life.It is important to build a good relationship with doctors, both primary care and specialist. Because of the rarity of the illness, many doctors will not have encountered it before. Each case of CIDP is different, and relapses, if they occur, may bring new symptoms and problems. Because of the variability in severity and progression of the disease, doctors will not be able to give a definite prognosis </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 Postoperative cognitive dysfunction and can you explain it in depth? [/INST] Postoperative cognitive dysfunction (POCD) is a decline in cognitive function (especially in memory and executive functions) that may last from 1–12 months after surgery, or longer. In some cases, this disorder may persist for several years after major surgery. POCD is distinct from emergence delirium. Its causes are under investigation and occurs commonly in older patients and those with pre-existing cognitive impairment.The causes of POCD are not understood. It does not appear to be caused by lack of oxygen or impaired blood flow to the brain and is equally likely under regional and general anesthesia. It may be mediated by the bodys inflammatory response to surgery.

Causes
The bodys inflammatory response to surgery likely plays an important role, at least in elderly patients. Various research initiatives during recent years have evaluated whether actions taken before, during and after surgery can lessen the possible deleterious effects of inflammation. For example, anti-inflammatory agents can be given before surgery. During surgery, inflammation can be modulated by temperature control, use of regional rather than general anesthesia or the use of beta blockers. After surgery, optimal pain management and infection control is important. Several studies have shown variable-significance positive effects when a multidisciplinary, multifactorial approach to elderly patient is followed during pre, peri and post-operative care.A Cochrane review explored whether inhalation anaesthetics or intravenous anaesthetics were more likely to cause POCD when used in the elderly for non-cardiac surgery.  Seven studies (869 participants) included in the review led to the conclusion that fewer people experienced POCD with total intravenous anaesthesia (TIVA) compared to inhalational anaesthesia.  The conclusions, however, rated "low" on GRADE scoring (confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect).

Assessment
Cognitive tests are given prior to operations to establish a baseline.  The same tests are again given post-operatively to determine the extent and duration of the decline for POCD. "A project examining adults 55 and older who have major non-cardiac surgeries is finding that upward of 30 percent of patients is testing significantly worse than their baseline 3 months later".

Epidemiology
POCD is common after cardiac surgery, and recent studies have now verified that POCD also exists after major non-cardiac surgery, although at a lower incidence. The risk of POCD increases with age, and the type of surgery is also important because there is a very low incidence associated with minor surgery. POCD is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 years or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery. Research interest has increased since early 2000, especially as more elderly patients are able to undergo successful minor and major surgeries.POCD has been studied through various institutions since the inception of the IPOCDS-I study centred in Eindhoven, Netherlands and Copenhagen, Denmark. This study found no causal relationship between cerebral hypoxia and low blood pressure and POCD. Age, duration of anaesthesia, introperative complications, and postoperative infections were found to be associated with POCD.
POCD is just as likely to occur after operations under regional anesthesia as under general anesthesia.
More likely after major operations than minor operations.
More likely after heart operations than other types of surgery.
More likely in aged than in younger patients.
More likely in older patients with high alcohol intake.
People with higher preoperative ASA physical status scores are more likely to develop POCD.
People with lower educational level are more likely to develop POCD than those with a higher educational level.
People with prior history of a stroke, even though there is complete functional recovery, are more likely to develop POCD.
More likely in the elderly with pre-existing declining mental functions, termed mild cognitive impairment (MCI). MCI is a transitional zone between normal mental function and evident Alzheimers disease or other forms of dementia. It is insidious, and seldom recognized, except in retrospect after affected persons are evidently demented.
Delirium and severe worsening of mental function is very likely in those with clinically evident Alzheimers disease or other forms of dementia, as well as those with a history of delirium after previous operations.

Footnotes
Further reading
"Postoperative cognitive dysfunction" (PDF). {{cite journal}}: Cite journal requires |journal= (help)
Muñoz-Corsini L, Gómez-Arnau J, Porras MC, Galindo S, Jiménez R (May 1997). "Postoperative cognitive dysfunction". Rev Esp Anestesiol Reanim. 44 (5): 191–200. PMID 9280997.
Crosby, Gregory; Culley, Deborah J. (2011). "Surgery and anesthesia: healing the body but harming the brain?". Anesthesia & Analgesia. 112 (5): 999–1001. doi:10.1213/ANE.0b013e3182160431. PMC 3092153. PMID 21515644.
Rasmussen, L. S. (November 1998). "Defining postoperative cognitive dysfunction". European Journal of Anaesthesiology </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 Pneumoretroperitoneum 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 Self-healing juvenile cutaneous mucinosis 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 Warthins tumor and can you explain it in depth? [/INST] Warthins tumor, also known as papillary cystadenoma lymphomatosum, is a benign cystic tumor of the salivary glands containing abundant lymphocytes and germinal centers (lymph node-like stroma). It is named for pathologist Aldred Scott Warthin, who described two cases in 1929.

Signs and symptoms
Warthins tumor primarily affects older individuals (age 60–70 years). There is a slight male predilection according to recent studies. The tumor is slow growing, painless, and usually appears in the tail of the parotid gland near the angle of the mandible. In 5–14% of cases, Warthins tumor is bilateral, but the two masses usually are at different times. Warthins tumor is highly unlikely to become malignant.

Locations
The gland most likely affected is the parotid gland </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 Pleuropulmonary blastoma and can you explain it in depth? [/INST] Pleuropulmonary blastoma (PPB) is a rare cancer originating in the lung or pleural cavity.  It occurs most often in infants and young children but also has been reported in adults.  In a retrospective review of 204 children with lung tumors, pleuropulmonary blastoma and carcinoid tumor were the most common primary tumors (83% of the 204 children had secondary tumors spread from cancers elsewhere in the body). Pleuropulmonary blastoma is regarded as malignant. The male:female ratio is approximately one.

Signs and symptoms
Symptoms may include coughing, an upper respiratory tract infection, shortness of breath, and chest pain.  These symptoms are very non-specific, and can be caused by other types of tumor in the lung or mediastinum more generally, and by other conditions </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 Susto and can you explain it in depth? [/INST] Susto (Spanish pronunciation: [ˈsusto], Portuguese pronunciation: [ˈsuʃtu]) is a cultural illness primarily among Latin American cultures.  It is described as a condition of "chronic somatic suffering stemming from emotional trauma or from witnessing traumatic experiences lived by others".

Symptoms
Among the indigenous peoples of Latin America, in which this illness is most common, susto may be conceptualized as a case of spirit attack. Symptoms of susto are thought to include nervousness, anorexia, insomnia, listlessness, fever, depression, and diarrhea.

Treatment
Treatments among indigenous people are natural. Some natural treatments to susto consist of using plants as medicine; sweating out the toxins; and massaging to encourage blood flow. Prayer is a big part of the treatment of susto. In addition to prayer, healing rituals are also used, some of which include sweeping and giving gifts.

Classification
Susto may be a culturally dependent variation of the symptoms of a panic attack, which is distinct from anxiety and depressive disorders.

See also
Psychological trauma

References
Further reading
Rubel, Arthur J (July 1964). "The Epidemiology of a Folk Illness: Susto in Hispanic America". Ethnology. 3 (3): 268–283. doi:10.2307/3772883. JSTOR 3772883. Also published as Chapter 12 in Landy, David, ed. (1977) </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 Drug-induced pigmentation 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 Colles fracture and can you explain it in depth? [/INST] A Colles fracture is a type of fracture of the distal forearm in which the broken end of the radius is bent backwards. Symptoms may include pain, swelling, deformity, and bruising. Complications may include damage to the median nerve.It typically occurs as a result of a fall on an outstretched hand. Risk factors include osteoporosis. The diagnosis may be confirmed via X-rays. The tip of the ulna may also be broken.Treatment may include casting or surgery. Surgical reduction and casting is possible in the majority of cases in people over the age of 50. Pain management can be achieved during the reduction with procedural sedation and analgesia or a hematoma block. A year or two may be required for healing to occur.About 15% of people have a Colles fracture at some point in their life. They occur more commonly in young adults and older people than in children and middle-aged adults. Women are more frequently affected than men. The fracture is named after Abraham Colles who described it in 1814.

Causes
The fracture is most commonly caused by people falling onto a hard surface and breaking their fall with outstretched hand (FOOSH)–falling with wrists flexed would lead to a Smiths fracture. Originally it was described in elderly and/or post-menopausal women. It usually occurs about three to five centimetres proximal to the radio-carpal joint with posterior and lateral displacement of the distal fragment resulting in the characteristic "dinner fork" or "bayonet" like deformity. Colles fracture is a common fracture in people with osteoporosis, second only to vertebral fractures.

Diagnosis
Diagnosis can be made upon interpretation of anteroposterior and lateral views alone.The classic Colles fracture has the following characteristics:
Transverse fracture of the radius
2.5 cm (0.98 inches) proximal to the radio-carpal joint
dorsal displacement and dorsal angulation, together with radial tiltOther characteristics:
Radial shortening
Loss of ulnar inclination≤
Radial angulation of the wrist
Comminution at the fracture site
Associated fracture of the ulnar styloid process in more than 60% of cases.

Classification
The term Colles fracture is classically used to describe a fracture at the distal end of the radius, at its cortico-cancellous junction. However, the term now tends to be used loosely to describe any fracture of the distal radius, with or without involvement of the ulna, that has dorsal displacement of the fracture fragments. Colles himself described it as a fracture that “takes place at about an inch and a half (38mm) above the carpal extremity of the radius” and “the carpus and the base of metacarpus appears to be thrown backward”. The fracture is sometimes referred to as a "dinner fork" or "bayonet" deformity due to the shape of the resultant forearm.Colles fractures can be categorized according to several systems including Frykman, Gartland & Werley, Lidström, Nissen-Lie and the Olders classifications.

Treatment
Management depends on the severity of the fracture. An undisplaced fracture may be treated with a cast alone </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 Self-defeating personality disorder and can you explain it in depth? [/INST] Self-defeating personality disorder (also known as masochistic personality disorder) was a proposed personality disorder </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 Fitz-Hugh–Curtis syndrome and can you explain it in depth? [/INST] Fitz-Hugh–Curtis syndrome is a rare complication of pelvic inflammatory disease (PID) involving liver capsule inflammation leading to the creation of adhesions. The condition is named after the two physicians, Thomas Fitz-Hugh, Jr and Arthur Hale Curtis who first reported this condition in 1934 and 1930 respectively.

Signs and symptoms
The major symptom and signs include an acute onset of right upper quadrant (RUQ) abdominal pain aggravated by breathing, coughing or laughing, which may be referred to the right shoulder.  There is usually also tenderness on palpation of the right upper abdomen and tenderness to percussion of the lower ribs which protect the liver.  Surprisingly there is often no or only minimal pelvic pain, vaginal discharge or cervical motion tenderness, which may lead to the diagnosis being missed.  This may be due to infectious bacteria bypassing pelvic structures on the way to the liver capsule.

Pathophysiology
Fitz-Hugh–Curtis syndrome occurs almost exclusively in women. It is usually caused by Chlamydia trachomatis (Chlamydia) or Neisseria gonorrhoeae (Gonorrhea) though other bacteria such as Bacteroides, Gardnerella, E. coli and Streptococcus have also been found to cause Fitz-Hugh-Curtis syndrome on occasion. These bacterial pathogens  cause a thinning of cervical mucus and allow bacteria from the vagina into the uterus and fallopian tubes, causing infection and inflammation. Occasionally, this inflammation can cause scar tissue to form on Glissons capsule, a thin layer of connective tissue surrounding the liver.(Bailey&Love)

Diagnosis
Abdominal ultrasound will typically be normal. Liver function tests will typically be normal or unchanged from baseline as the infection does not involve the liver parenchyma. If a D-dimer is ordered, which it often is when there is pleuritic torso pain, it will usually be markedly elevated but other testing for pulmonary embolism will be normal. CT of the abdomen with IV contrast may show subtle enhancement of the liver capsule, but this may be missed by radiologists if they are not advised to look for it </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 Ornithine transcarbamylase deficiency and can you explain it in depth? [/INST] Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females.
In severely affected individuals, ammonia concentrations increase rapidly causing ataxia, lethargy and death without rapid intervention. OTC deficiency is diagnosed using a combination of clinical findings and biochemical testing, while confirmation is often done using molecular genetics techniques.
Once an individual has been diagnosed, the treatment goal is to avoid precipitating episodes that can cause an increased ammonia concentration. The most common treatment combines a low protein diet with nitrogen scavenging agents. Liver transplant is considered curative for this disease. Experimental trials of gene therapy using adenoviral vectors resulted in the death of one participant, Jesse Gelsinger, and have been discontinued.

Signs and symptoms
As with several other metabolic conditions, OTC deficiency can have variable presentations, regarding age of onset and the severity of symptoms. This compounded when considering heterozygous females and the possibility of non-random X-inactivation. In the classic and most well-known presentation, a male infant appears well initially, but by the second day of life they are irritable, lethargic and stop feeding. A metabolic encephalopathy develops, and this can progress to coma and death without treatment. Ammonia is only toxic to the brain, other tissues can handle elevated ammonia concentrations without problems.Later onset forms of OTC deficiency can have variable presentations. Although late onset forms of the disease are often considered milder than the classic infantile presentation, any affected individual is at risk for an episode of hyperammonemia that could still be life-threatening, if presented with the appropriate stressors. These patients will often present with headaches, nausea, vomiting, delayed growth and a variety of psychiatric symptoms (confusion, delirium, aggression, or self-injury). A detailed dietary history of an affected individual with undiagnosed OTC deficiency will often reveal a history of protein avoidance.The prognosis of a patient with severe OTC deficiency is well correlated with the length of the hyperammonemic period rather than the degree of hyperammonemia or the presence of other symptoms, such as seizures. Even for patients with late onset forms of the disease, their overall clinical picture is dependent on the extent of hyperammonemia they have experienced, even if it has remained unrecognized.

Genetics
OTC deficiency is caused by mutations in the OTC gene, which is located on the X chromosome. OTC codes for the mitochondrial enzyme ornithine transcarbamylase, which is expressed only in liver. The functional enzyme consists of three identical subunits. OTC is the last enzyme in the proximal portion of the urea cycle, which consists of the reactions that take place in the mitochondria. The substrates of the reaction catalyzed by ornithine transcarbamylase are ornithine and carbamyl phosphate, while the product is citrulline.There are no common mutations that cause disease, however 10 - 15% of disease causing mutations are deletions. It is inherited in an X-linked recessive manner, meaning males are more commonly affected than females. Females who carry a defective copy of the gene can be severely affected or asymptomatic, largely depending on the random nature of X-inactivation. There is some degree of genotype - phenotype correlation with OTC deficiency, but this depends on a number of situations. Individuals with milder mutations, often associated with late onset disease can still present with severe illness when exposed to sufficient metabolic stress. Correlations are more difficult to ascertain in females, since the residual activity of OTC in the liver is impacted not only by the nature of the mutation, but also by the random pattern of X-inactivation. OTC deficiency is estimated to be the most common urea cycle disorder. An exact incidence is difficult to calculate, due to the varying clinical presentations of later onset forms of the disease. Early estimates of the incidence were as high as 1:14,000 live births, however later studies have decreased these estimates to approximately 1:60,000 - 1:72,000.

Diagnosis
In individuals with marked hyperammonemia, a urea cycle disorder is usually high on the list of possible causes. While the immediate focus is lowering the patients ammonia concentrations, identifying the specific cause of increased ammonia levels is key as well.
Diagnostic testing for OTC deficiency, or any individual with hyperammonemia involves plasma and urine amino acid analysis, urine organic acid analysis (to identify the presence or absence of orotic acid, as well as rule out an organic acidemia) and plasma acylcarnitines (will be normal in OTC deficiency, but can identify some other causes of hyperammonemia). An individual with untreated OTC deficiency will show decreased citrulline and arginine concentrations (because the enzyme block is proximal to these intermediates) and increased orotic acid. The increased orotic acid concentrations result from the buildup of carbamoyl phosphate. This biochemical phenotype (increased ammonia, low citrulline and increased orotic acid) is classic for OTC deficiency, but can also be seen in neonatal presentations of ornithine aminotransferase deficiency. Only severely affected males consistently demonstrate this classic biochemical phenotype.
Heterozygous females can be difficult to diagnose. With the rise of sequencing techniques, molecular testing has become preferred, particularly when the disease causing mutations in the family are known. Historically, heterozygous females were often diagnosed using an allopurinol challenge. In a female with reduced enzyme activity, an oral dose of allopurinol would be metabolized to oxypurinol ribonucleotide, which blocks the pyrimidine biosynthetic pathway. When this induced enzymatic block is combined with reduced physiologic enzyme activity as seen in heterozygotes, the elevation of orotic acid could be used to differentiate heterozygotes from unaffected individuals. This test was not universally effective, as it had both false negative and false positive results.Ornithine transcarbamylase is only expressed in the liver, thus performing an enzyme assay to confirm the diagnosis requires a liver biopsy. Before molecular genetic testing was commonly available, this was one of the only methods for confirmation of a suspected diagnosis. In cases where prenatal diagnosis was requested, a fetal liver biopsy used to be required to confirm if a fetus was affected. Modern molecular techniques have eliminated this need, and gene sequencing is now the preferred method of diagnosis in asymptomatic family members after the diagnosis has been confirmed in a proband.

Treatment
The treatment goal for individuals affected with OTC deficiency is the avoidance of hyperammonemia. This can be accomplished through a strictly controlled low-protein diet, as well as preventative treatment with nitrogen scavenging agents such as sodium benzoate </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 Perifollicular fibroma 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 Spinal muscular atrophy with lower extremity predominance 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 Shunt nephritis and can you explain it in depth? [/INST] Shunt nephritis is a rare disease of the kidney that can occur in patients being treated for hydrocephalus with a cerebral shunt. It usually results from an infected shunt that produces a long-standing blood infection, particularly by the bacterium Staphylococcus epidermidis. Kidney disease results from an immune response that deposits immune complexes in the kidney. The most common signs and symptoms of the condition are blood and protein in the urine, anemia, and high blood pressure. Diagnosis is based on these findings in the context of characteristic laboratory values. Treatment includes antibiotics and the prompt removal of the infected shunt. Over half of individuals with shunt nephritis recover completely; most of the remainder have some degree of persistent kidney disease.

Presentation
The clinical presentation of shunt nephritis is variable, but the most common manifestations of shunt nephritis include blood in the urine, protein in the urine, anemia, and high blood pressure. Recurrent fever, enlarged liver and spleen, and a skin rash may also be present. Rarely, the major complaint may be arthritis.

Pathophysiology
Shunt nephritis occurs when a shunt becomes infected with bacteria, most commonly Staphylococcus epidermidis. Bacteria from this infected shunt seed the bloodstream, leading to blood infection (bacteremia). In response to long-standing infection (months to years), the body mounts an immune response that results in deposition of immune complexes in the kidney, leading to nephritis.

Diagnosis
Urinalysis typically demonstrates hematuria and proteinuria. Levels of the complement protein C3 are low, while levels of C-reactive protein and cryoglobulins may be modestly elevated </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 Fountain syndrome and can you explain it in depth? [/INST] Fountain syndrome is an autosomal recessive congenital disorder characterized by mental retardation, deafness, skeletal abnormalities and a coarse face with full lips. The abnormal swelling of the cheeks and lips are due to the excessive accumulation of body fluids under the skin. The deafness is due to malformation of the cochlea structure within the inner ear.

Signs and symptoms
Cause
The exact cause of the disorder is unknown, but it is believed to be inherited in an autosomal recessive manner.

Diagnosis
Fountain syndrome is usually diagnosed in infancy or early childhood. It can be diagnosed by thorough clinical evaluation, characteristic physical findings, and specialized tests such as audiological tests and scans of the inner ear and brain.

Treatment
Unfortunately, there is not one specific treatment option that can rid a person of this syndrome. However, there are many routes one can take to make living with this disease a lot easier. For example, there are many treatment programs that doctors can specialize for patients and their needs. Meeting with a doctor is very crucial and these specializations can be very useful. Also, one can seek help from pediatricians, EENT doctors, audiologists, and orthopedists. Brace fittings, hearing aids, and physical therapy can also be pushed by ones doctor, so that a patient can live normally. Additionally, anticonvulsant drugs can be used to stop seizures.

References
Fountain RB (1974). "Familial bone abnormalities, deaf mutism, mental retardation and skin granuloma". Proc R Soc Med. 67 (9): 878–879. PMC 1645940. PMID 4431800.
Fryns JP (1989). "Fountains syndrome: mental retardation, sensorineural deafness, skeletal abnormalities, and coarse face with full lips". J Med Genet. 26 (11): 722–724. doi:10.1136/jmg.26.11.722. PMC 1015742. PMID 2585470.
Fryns JP, Dereymaeker A, Hoefnagels M, Van den Berghe H (1987). "Mental retardation, deafness, skeletal abnormalities, and coarse face with full lips: confirmation of the Fountain syndrome". Am J Med Genet. 26 (3): 551–555. doi:10.1002/ajmg.1320260307 </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 Nasopharyngeal angiofibroma and can you explain it in depth? [/INST] Nasopharyngeal angiofibroma is an angiofibroma also known as juvenile nasal angiofibroma, fibromatous hamartoma, and angiofibromatous hamartoma of the nasal cavity. It is a histologically benign but locally aggressive vascular tumor of the nasopharynx that  arises from the superior margin of the sphenopalatine foramen and grows in the back of the nasal cavity. It most commonly affects adolescent males (because it is a hormone-sensitive tumor).
Though it is a benign tumor, it is locally invasive and can invade the nose, cheek, orbit (frog face deformity), or brain. Patients with nasopharyngeal angiofibroma usually present with one-sided nasal obstruction with profuse epistaxis.

Signs and symptoms
Frequent chronic epistaxis or blood-tinged nasal discharge
Nasal obstruction and rhinorrhea
Facial dysmorphism (when locally invasive)
Conductive hearing loss from eustachian-tube obstruction
Diplopia, which occurs secondary to erosion into superior orbital fissure and due to third and sixth nerve palsy.
Proptosis when having intraorbital extension.
Rarely anosmia, recurrent otitis media, and eye pain.

Diagnosis
If nasopharyngeal angiofibroma is suspected based on physical examination (a smooth vascular submucosal mass in the posterior nasal cavity of an adolescent male), imaging studies such as CT or MRI should be performed </s>