<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 Chorioamnionitis and can you explain it in depth? [/INST] Chorioamnionitis, also known as intra-amniotic infection (IAI), is inflammation of the fetal membranes (amnion and chorion), usually due to bacterial infection. In 2015, a National Institute of Child Health and Human Development Workshop expert panel recommended use of the term "triple I" to address the heterogeneity of this disorder. The term triple I refers to intrauterine infection or inflammation or both and is defined by strict diagnostic criteria, but this terminology has not been commonly adopted although the criteria are used.Chorioamnionitis results from an infection caused by bacteria ascending from the vagina into the uterus and is associated with premature or prolonged labor. It triggers an inflammatory response to release various inflammatory signaling molecules, leading to increased prostaglandin and metalloproteinase release. These substances promote uterine contractions and cervical ripening, causations of premature birth. The risk of developing chorioamnionitis increases with number of vaginal examinations performed in the final month of pregnancy, including labor. Tobacco and alcohol use also puts mothers at risk for chorioamnionitis development.Chorioamnionitis is caught early by looking at signs and symptoms such as fever, abdominal pain, or abnormal vaginal excretion. Administration of antibiotics if the amniotic sac bursts prematurely can prevent chorioamnionitis occurrence.

Signs and symptoms
The signs and symptoms of clinical chorioamnionitis include fever, leukocytosis (>15,000 cells/mm³), maternal (>100 bpm) or fetal (>160 bpm) tachycardia, uterine tenderness and preterm rupture of membranes.

Causes
Causes of chorioamnionitis stem from bacterial infection as well as obstetric and other related factors.

Microorganisms
Bacterial, viral, and even fungal infections can cause chorioamnionitis. Most commonly from Ureaplasma, Fusobacterium, and Streptococcus bacteria species. Less commonly, Gardnerella, Mycoplasma, and Bacteroides bacteria species. Sexually transmitted infections, chlamydia and gonorrhea, can cause development of the condition as well. Studies are continuing to identify other microorganism classes and species as infection sources.

Obstetric and other
Birthing-related events, lifestyle, and ethnic background have been linked to an increase in the risk of developing chorioamnionitis apart from bacterial causation. Premature deliveries, ruptures of the amniotic sac membranes, prolonged labor, and primigravida childbirth are associated with this condition. At term mothers who experience a combination of pre-labor membrane ruptures and multiple invasive vaginal examinations, prolonged labor, or have meconium appear in the amniotic fluid are at higher risk than at term mothers experiencing just one of those events. In other studies, smoking, alcohol use and drug use are noted as risk factors. Those of African American ethnicity are noted to be at higher risk.

Anatomy
The amniotic sac consists of two parts:

The outer membrane is the chorion. It is closest to the mother and physically supports the much thinner amnion.
The chorion is the last and outermost of the membranes that make up the amniotic sac.
The inner membrane is the amnion. It is in direct contact with the amniotic fluid, which surrounds the fetus.
The amniotic fluid exists within the amnion, and is where the fetus is able to grow and develop.
The swelling of the amnion and chorion is characteristic of chorioamnionitis, occurring when bacteria makes its way into the amniotic fluid and creates an infection within the amniotic fluid.

Diagnosis
Pathologic
Chorioamnionitis is diagnosed from a histologic (tissue) examination of the fetal membranes. Confirmed histologic chorioamnionitis without any clinical symptoms is termed subclinical chorioamnionitis and is more common than symptomatic clinical chorioamnionitis.Infiltration of the chorionic plate by neutrophils is diagnostic of (mild) chorioamnionitis. More severe chorioamnionitis involves subamniotic tissue and may have fetal membrane necrosis and/or abscess formation.Severe chorioamnionitis may be accompanied by vasculitis of the umbilical blood vessels due to the fetus inflammatory cells. If very severe, funisitis, inflammation of the umbilical cord connective tissue, occurs.

Suspected clinical diagnosis
The presence of fever between 38.0°C and 39.0°C alone is insufficient to indicate chorioamnionitis and is termed isolated maternal fever. Isolated maternal fever may not have an infectious cause and does not required antibiotic treatment.When intrapartum (during delivery) fever is higher than 39.0°C, suspected diagnosis of chorioamnionitis can be made. Alternatively, if intrapartum fever is between 38.0°C and 39.0°C, an additional risk factor must be present to make a presumptive diagnosis of chorioamnionitis. Additional risk factors include:
Fetal tachycardia
Maternal leukocytosis (>15,000 cells/mm³)
Purulent cervical drainage

Confirmed diagnosis
Diagnosis is typically not confirmed until after delivery. However, people with confirmed diagnosis and suspected diagnosis have the same post-delivery treatment regardless of diagnostic status. Diagnosis can be confirmed histologically or through amniotic fluid tests such as gram staining, glucose levels, or other culture results consistent with infection.

Prevention
If the amniotic sac breaks early into pregnancy, the potential of introducing bacteria in the amniotic fluid can increase. Administering antibiotics maternally can potentially prevent chorioamnionitis and allow for a longer pregnancy. In addition, it has been shown that it is not necessary to deliver the fetus quickly after chorioamnionitis is diagnosed, so a C-section is not necessary unless maternal health concern is present. However, research has found that beginning labor early at approximately 34 weeks can lessen the likelihood of fetal death, and reduce the potential for excessive infection within the mother.In addition, providers should interview people suspected to have chorioamnionitis about whether they are experiencing signs and symptoms at scheduled obstetrics visits during pregnancy, including whether the individual has experienced excretion vaginally, febrile, or abdominal pain.

Treatment
The American College of Obstetricians and Gynecologists Committee Opinion proposes the use of antibiotic treatment in intrapartum mothers with suspected or confirmed chorioamnionitis and maternal fever without an identifiable cause.Intrapartum antibiotic treatment consists of:
Standard
Ampicillin + gentamicin
Alternative
Ampicillin/sulbactam
Ticarcillin/clavulanate
Cefoxitine
Cefotetan
Piperacillin/tazobactam
Ertapenem
Cesarean delivery
Ampicillin and gentamicin plus either clindamycin or metronidazole
Penicillin-allergy
Vancomycin + gentamicin
Gentamicin + clindamycinHowever, there is not enough evidence to support the most efficient antimicrobial regimen. Starting the treatment during the intrapartum period is more effective than starting it postpartum; it shortens the hospital stay for the mother and the neonate. There is currently not enough evidence to dictate how long antibiotic therapy should last. Completion of treatment/cure is only considered after delivery.

Supportive measures
Acetaminophen is often used for treating fevers and may be beneficial for fetal tachycardia. There can be increased likelihood for neonatal encephalopathy when mothers have intrapartum fever.

Outcomes
Chorioamnionitis has possible associations with numerous neonatal conditions. Intrapartum (during labor) chorioamnionitis may be associated with neonatal pneumonia, meningitis, sepsis, and death. Long-term infant complications like bronchopulmonary dysplasia, cerebral palsy, and Wilson-Mikity syndrome have been associated to the bacterial infection. Furthermore, histological chorioamnionitis may increase the likelihood of newborn necrotizing enterocolitis, where one or more sections of the bowel die. This occurs when the fetal gut barrier becomes compromised and is more susceptible to conditions like infection and sepsis. In addition, chorioamnionitis can act as a risk factor for premature birth and periventricular leukomalacia.

Complications
For mother and fetus, chorioamnionitis may lead to short-term and long-term issues when microbes move to different areas or trigger inflammatory responses due to infection.

Maternal complications
Higher risk for C-section
Postpartum hemorrhage
Endometritis
Bacteremia (often due to Group B streptococcus and Escherichia coli)
Pelvic abscessMothers with chorioamnionitis who undergo a C-section may be more likely to develop pelvic abscesses, septic pelvic thrombophlebitis, and infections at the surgical site.

Fetal complications
Fetal death
Neonatal sepsis

Neonatal complications
Perinatal death
Asphyxia
Early onset neonatal sepsis
Septic shock
Neonatal pneumonia
Infant respiratory distressIn the long-term, infants may be more likely to experience cerebral palsy or neurodevelopmental disabilities </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 Gray baby syndrome and can you explain it in depth? [/INST] Gray baby syndrome (also termed Gray or Grey syndrome) is a rare but serious, even fatal, side effect that occurs in newborn infants (especially premature babies) following the accumulation of antibiotic chloramphenicol. Chloramphenicol is a broad-spectrum antibiotic that has been used to treat a variety of bacteria infections like Streptococcus pneumoniae as well as typhoid fever, meningococcal sepsis, cholera, and eye infections. Chloramphenicol works by binding to ribosomal subunits which blocks transfer ribonucleic acid and prevents the synthesis of bacterial proteins. Chloramphenicol has also been used to treat neonates born before 37 weeks of the gestational period for prophylaxis purposes. In 1958, newborns born prematurely due to rupture of the amniotic sac were given chloramphenicol to prevent possible infections, and it was noticed that these newborns had a higher mortality rate compared with those who were not treated with the antibiotic. Over the years, chloramphenicol has been used less in clinical practices due to the risks of toxicity not only to neonates, but also to adults due to the risk of aplastic anemia. Chloramphenicol is now reserved to treat certain severe bacteria infections that were not successfully treated with other antibiotic medications. Signs and symptoms are summarized in the WHO Model Formulary for Children 2010 under the rare adverse effect section of chloramphenicol.

Signs and symptoms
Since the syndrome is due to the accumulation of chloramphenicol, the signs and symptoms are dose related. According to Kastens review published in the Mayo Clinic Proceedings, a serum concentration of more than 50 μg/mL is a warning sign, while Hammett-Stabler and John states that the common therapeutics peak level is 10-20 μg/mL and is expected to achieve after 0.5-1.5 hours of intravenous administration in their review of antimicrobial drugs. The common onset of signs and symptoms are 2 to 9 days after the initiation of the medication, which allows the serum concentration to build up to reach the toxic concentration above. Common signs and symptoms include loss of appetite, fussiness, vomiting, ashen gray color of the skin, hypotension (low blood pressure), cyanosis (blue discoloration of lips and skin), hypothermia, cardiovascular collapse, hypotonia (muscle stiffness), abdominal distension, irregular respiration, and increased blood lactate.

Pathophysiology
Two pathophysiologic mechanisms are thought to play a role in the development of gray baby syndrome after exposure to chloramphenicol. This condition is due to a lack of glucuronidation reactions occurring in the baby (phase II hepatic metabolism), thus leading to an accumulation of toxic chloramphenicol metabolites:
Metabolism: The UDP-glucuronyl transferase enzyme system in infants, especially premature infants, is not fully developed and incapable of metabolizing the excessive drug load needed to excrete chloramphenicol.
Elimination: Insufficient renal excretion of the unconjugated drug.Insufficient metabolism and excretion of chloramphenicol leads to increased blood concentrations of the drug, causing blockade of the electron transport of the liver, myocardium, and skeletal muscles. Since the electron transport is an essential part of cellular respiration, its blockade can result in cell damage. In addition, the presence of chloramphenicol weakens the binding of bilirubin and albumin, so increased levels of the drug can lead to high levels of free bilirubin in the blood, resulting in brain damage or kernicterus. If left untreated, possible bleeding, renal (kidney) and/or hepatic (liver) failure, anemia, infection, confusion, weakness, blurred vision, or eventually death are expected. Additionally, chloramphenicol is significantly insoluble due to an absence of acidic and basic groups in its molecular compound. As a result, larger amounts of the medication are required to achieve the desired therapeutic effect. High volumes of a medication that can cause various toxicities is another avenue how chloramphenicol can potentially lead to grey baby syndrome.

Diagnosis
Gray baby syndrome should be suspected in a new born with abdominal distension, progressive pallid cyanosis, irregular respirations, and refusal to breastfeed. The cause of gray baby syndrome can come from the direct use of intravenous or oral chloramphenicol in neonates. Direct chronological relation between the use of the medication and signs and symptoms of the syndrome should be found in the previous medical history. In terms of the possible route of chloramphenicol, gray baby syndrome may not come from the mothers use of chloramphenicol during pregnancy or breastfeeding. According to the Drug and Lactation database (LactMed), it states that "milk concentrations are not sufficient to induce gray baby syndrome". It is also reported that the syndrome may not develop in infants when their mothers use the medication in their late period of pregnancy. According to the Oxford Review, chloramphenicol given to mothers during their pregnancy did not result in gray baby syndrome, but was caused by infants receiving supra-therapeutic doses of chloramphenicol after birth. The presentation of symptoms can depend on the level of exposure of the drug to the baby, given its dose-related nature. A broad diagnosis is usually needed for babies who present with cyanosis. To support the diagnosis, blood work should be done to determine the level of serum chloramphenicol, and to further evaluate chloramphenicol toxicity, a complete blood panel including levels of serum ketones, glucose (due to the risk of hypoglycemia), metabolic panel should be completed to help determine if an infant has the syndrome. Other tools used to help with diagnosis include CT scans, ultrasound, and electrocardiogram.

Prevention
Since the syndrome is a side effect of chloramphenicol, the prevention is primarily related to the proper use of the medication. The WHO Model Formulary for Children 2010 recommends to reserve chloramphenicol for life-threatening infections. As well as using chloramphenicol only when necessary, it should also be used in short periods of time to also prevent the potential for toxicity. In particular, this medication should not be prescribed especially in neonates less than one week old due to the significant risk of toxicity. Preterm infants especially should not be administered chloramphenicol. Gray baby syndrome has been noted to be dose-dependent as it typically occurs in neonates who have received a daily dose greater than 200 milligrams.When chloramphenicol is necessary, the condition can be prevented by using chloramphenicol at the recommended doses and monitoring blood levels, or alternatively, third generation cephalosporins can be effectively substituted for the drug, without the associated toxicity. Also, repeated course of administration and prolonged treatment should be avoided as much as possible. In terms of hepatic development in neonates, it take only weeks from birth for them to develop their UDPGT expression and function to be at an adult-like level, while the function is only about 1% in the late pregnancy, even right before birth-giving. According to MSD Manuals, chloramphenicol should not be given to neonates with younger than 1 month of age with more than a dose of 25 mg/kg/day to start with. The serum concentration of the medication should be monitored to titrate to a therapeutic level and to prevent toxicity. Medication reconciliation of other medications that neonates may be taking that can decrease blood cell count should be monitored because of this medications ability to suppress bone marrow activity.  Rifampicin and trimethoprim are examples of medications with bone marrow suppression abilities and are contraindicated for concomitant use with chloramphenicol. In regards to bone marrow suppression, chloramphenicol has two major etiological manifestations. The first mechanism of bone marrow suppression affects the formation of blood cells such as erythrocytes, and this can be reversible since it is an early sign up toxicity. The second form of bone marrow suppression is bone marrow aplasia, which is associated with being late into toxicity and cannot be reversed in some cases. Chloramphenicol is contraindicated in persons who are breastfeeding due to the risk of toxic effects in the baby, but if maternal use of chloramphenicol cannot be avoided, close monitoring of the babys symptoms such as feeding difficulties, and blood work is recommended.

Treatment
Chloramphenicol therapy should be stopped immediately if objective or subjective signs of gray baby syndrome are suspected since gray baby syndrome can be fatal for the infant if it is not diagnosed early on as it can lead to anemia, shock, and end-organ damage </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 Spasticity and can you explain it in depth? [/INST] Spasticity  (from Greek  spasmos- drawing, pulling) is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles.
Clinically, spasticity results from the loss of inhibition of motor neurons, causing excessive velocity-dependent muscle contraction. This ultimately leads to hyperreflexia, an exaggerated deep tendon reflex. Spasticity is often treated with the drug baclofen, which acts as an agonist at GABA receptors, which are inhibitory.
Spastic cerebral palsy is the most common form of cerebral palsy, which is a group of permanent movement problems that do not get worse over time. GABAs inhibitory actions contribute to baclofens efficacy as an anti-spasticity agent.

Cause
Spasticity mostly occurs in disorders of the central nervous system (CNS) affecting the upper motor neurons in the form of a lesion, such as spastic diplegia, or upper motor neuron syndrome, and can also be present in various types of multiple sclerosis, where it occurs as a symptom of the progressively-worsening attacks on myelin sheaths and is thus unrelated to the types of spasticity present in neuromuscular cerebral palsy rooted spasticity disorders.The cause of spasticity is thought to be where an imbalance occurs in the excitatory and inhibitory input to α motor neurons caused by damage to the spinal cord and/or central nervous system.  The damage causes a change in the balance of signals between the nervous system and the muscles, leading to increased excitability in  muscles. This is common in people who have cerebral palsy, brain injuries or a spinal cord injury, but it can happen to anybody e.g. having a stroke.One factor that is thought to be related to spasticity is the stretch reflex. This reflex is important in coordinating normal movements in which muscles are contracted and relaxed and in keeping the muscle from stretching too far. Although the result of spasticity is problems with the muscles, spasticity is actually caused by an injury to a part of the central nervous system (the brain or spinal cord) that controls voluntary movements. The damage causes a change in the balance of signals between the nervous system and the muscles. This imbalance leads to increased activity (excitability) in the muscles.  Receptors in the muscles receive messages from the nervous system, which sense the amount of stretch in the muscle and sends that signal to the brain.  The brain responds by sending a message back to reverse the stretch by contracting or shortening.Overall, a defining feature of spasticity is that the increased resistance to passive stretch is velocity-dependent. Lance (1980) describes it this way:  "...a motor disorder, characterised by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex as one component of the upper motor neurone (UMN) syndrome".Spasticity is found in conditions where the brain and/or spinal cord are damaged or fail to develop normally; these include cerebral palsy, multiple sclerosis, spinal cord injury and acquired brain injury including stroke. Damage to the CNS as a result of stroke or spinal cord injury, alter the [net inhibition] of peripheral nerves in the affected region. This change in input to bodily structures tends to favor excitation and therefore increase nerve excitability. CNS damage also causes nerve cell membranes to rest in a more [depolarized] state. The combination of decreased inhibition and an increased depolarized state of cell membranes, decreases action potential threshold for nerve signal conduction, and thus increases activity of structures innervated by the affected nerves (spasticity). Muscles affected in this way have many other potential features of altered performance in addition to spasticity, including muscle weakness; decreased movement control; clonus (a series of involuntary rapid muscle contractions often symptomatic of muscle over-exertion and/or muscle fatigue); exaggerated deep tendon reflexes; and decreased endurance.

Spasticity and clonus
Clonus (i.e. involuntary, rhythmic, muscular contractions and relaxations) tends to co-exist with spasticity in many cases of stroke and spinal cord injury likely due to their common physiological origins. Some consider clonus as simply an extended outcome of spasticity. Although closely linked, clonus is not seen in all patients with spasticity. Clonus tends to not be present with spasticity in patients with significantly increased muscle tone, as the muscles are constantly active and therefore not engaging in the characteristic on/off cycle of clonus. Clonus results due to an increased motor neuron excitation (decreased action potential threshold) and is common in muscles with long conduction delays, such as the long reflex tracts found in distal muscle groups. Clonus is commonly seen in the ankle but may exist in other distal structures as well, such as the knee or spine.

Diagnosis
The clinical underpinnings of two of the most common spasticity conditions, spastic cerebral palsy and multiple sclerosis, can be described as follows: in spastic diplegia, the upper motor neuron lesion arises often as a result of neonatal asphyxia, while in conditions like multiple sclerosis, spasticity is thought by some to be as a result of the autoimmune destruction of the myelin sheaths around nerve endings—which in turn can mimic the gamma amino butyric acid deficiencies present in the damaged nerves of spastic cerebral palsy children, leading to roughly the same presentation of spasticity, but which clinically is fundamentally different from the latter.Spasticity is assessed by feeling the resistance of the muscle to passive lengthening in its most relaxed state. A spastic muscle will have immediately noticeable, often quite forceful, increased resistance to passive stretch when moved with speed and/or while attempting to be stretched out, as compared to the non-spastic muscles in the same persons body (if any exist). As there are many features of the upper motor neuron syndrome, there are likely to be multiple other changes in affected musculature and surrounding bones, such as progressive malalignments of bone structure around the spastic muscles (leading for example to the scissor gait and tip-toeing gait due to ankle equinus or ankle planter flexion deformity in spastic cerebral palsy children. scissor gait is caused by spasticity of the hip adductor muscles while tip-toeing gait is caused by spasticity of the gastrocnemius-soleus muscle complex or calf musculature.  Also, following an upper motor neuron lesion, there may be multiple muscles affected, to varying degrees, depending on the location and severity of the upper motor neuron damage. The result for the affected individual, is that they may have any degree of impairment, ranging from a mild to a severe movement disorder.  A relatively mild movement disorder may contribute to a loss of dexterity in an arm, or difficulty with high level mobility such as running or walking on stairs.  A severe movement disorder may result in marked loss of function with minimal or no volitional muscle activation. There are several scales used to measure spasticity, such as the Kings hypertonicity scale, the Tardieu, and the modified Ashworth. Of these three, only the Kings hypertonicity scale measures a range of muscle changes from the UMN lesion, including active muscle performance as well as passive response to stretch.Assessment of a movement disorder featuring spasticity may involve several health professionals depending on the affected individuals situation, and the severity of their condition. This may include physical therapists, physicians (including neurologists and rehabilitation physicians), orthotists and occupational therapists. Assessment is needed of the affected individuals goals, their function, and any symptoms that may be related to the movement disorder, such as pain. A thorough assessment will include analysis of posture, active movement, muscle strength, movement control and coordination, and endurance, as well as spasticity (response of the muscle to stretch). Spastic muscles typically demonstrate a loss of selective movement, including a loss of eccentric control (decreased ability to actively lengthen). While multiple muscles in a limb are usually affected in the upper motor neuron syndrome, there is usually an imbalance of activity, such that there is a stronger pull in one direction, such as into elbow flexion. Decreasing the degree of this imbalance is a common focus of muscle strengthening programs. Spastic movement disorders also typically feature a loss of stabilisation of an affected limb or the head from the trunk, so a thorough assessment requires this to be analysed as well.Secondary effects are likely to impact on assessment of spastic muscles. If a muscle has impaired function following an upper motor neuron lesion, other changes such as increased muscle stiffness are likely to affect the feeling of resistance to passive stretch. Other secondary changes such as loss of muscle fibres following acquired muscle weakness are likely to compound the weakness arising from the upper motor neuron lesion. In severely affected spastic muscles, there may be marked secondary changes, such as muscle contracture, particularly if management has been delayed or absent.

Treatment
Treatment should be based on assessment by relevant health professionals.  For spastic muscles with mild-to-moderate impairment, exercise should be the mainstay of management, and is likely needed to be prescribed by a Physiatrist (Doctor specialized in Rehabilitation medicine), occupational therapist, physical therapist, accredited exercise physiologist (AEP) or other health professional skilled in neurological rehabilitation.Muscles with severe spasticity are likely to be more limited in their ability to exercise, and may require help to do this. In spastic cerebral palsy children the main treatment modality of spasticity is conservative in the form of botulinum toxin A injection and various physical therapy modalities such as serial casting, sustained stretching and medical pharmacologic treatment. Spasticity in cerebral palsy children is usually generalized although with varying degrees of severity across the affected extremities and trunk musculature. Neglected or inappropriately treated spasticity can eventually lead to joint contractures. Both spasticity and contractures can cause joint subluxations or dislocations and severe gait difficulties. In the event of contracture there is no role for conservative treatment. Hip dislocation and ankle equinus deformity are known to arise from muscle spasticity primarily. Orthopedic surgical reconstruction of the hip is commonly practiced to improve sitting balance, nursing care and relief hip pain.
Treatment should be done with firm and constant manual contact positioned over nonspastic areas to avoid stimulating the spastic muscle(s). Alternatively, rehabilitation robotics can be used to provide high volumes of passive or assisted movement, depending on the individuals requirements; this form of therapy can be useful if therapists are at a premium, and has been found effective at reducing spasticity in patients with strokes.  For muscles that lack any volitional control, such as after complete spinal cord injury, exercise may be assisted, and may require equipment, such as using a standing frame to sustain a standing position. A general treatment guideline can be followed that involves:

The initial focus on first activating contraction of antagonist muscles to provide reciprocal inhibition and lengthen spastic muscles
Reciprocal actions are attempted. Agonist contractions are performed first in small ranges progressing to larger arcs of movement
Highly stressful activities be minimized early in training
Functional skills are targeted for training
Patients and family/caregivers should be educated about the importance of maintaining range of motion and doing daily exercisesMedical interventions may include such medications as baclofen, diazepam, dantrolene, or clonazepam. Phenol injections can be used, or botulinum toxin injections into the muscle belly, to attempt to dampen the signals between nerve and muscle. The effectiveness of medications vary between individuals, and vary based on location of the upper motor neuron lesion (in the brain or the spinal cord). Medications are commonly used for spastic movement disorders, but research has not shown functional benefit for some drugs. Some studies have shown that medications have been effective in decreasing spasticity, but that this has not been accompanied by functional benefits. Surgery could be required for a tendon release in the case of a severe muscle imbalance leading to contracture. In spastic CP, selective dorsal rhizotomy has also been used to decrease muscle overactivity.Incorporating hydrotherapy in the treatment program may help decrease spasm severity, promote functional independence, improve motor recovery and decrease medication required for spasticity, which may help reduce the side effects that are possible with oral drug treatments.   A 2004 study compared the effects of hydrotherapy on spasticity, oral baclofen dosage and Functional Independence Measure (FIM) scores of patients with a spinal cord injury (SCI). It was found that subjects who received hydrotherapy treatment obtained increased FIM scores and a decreased intake of oral baclofen medication.  A 2009 study looked at the effect of hydrotherapy to decrease spasticity on post-stroke, hemiparetic patients with limited mobility and concluded that there was a significantly larger increase in FIM scores compared to the control group that did not receive hydrotherapy.

Prognosis
The prognosis for those with spastic muscles depends on multiple factors, including the severity of the spasticity and the associated movement disorder, access to specialised and intensive management, and ability of the affected individual to maintain the management plan (particularly an exercise program).  Most people with a significant UMN lesion will have ongoing impairment, but most of these will be able to make progress. The most important factor to indicate ability to progress is seeing improvement, but improvement in many spastic movement disorders may not be seen until the affected individual receives help from a specialised team or health professional.

Research
Doublecortin positive cells, similar to stem cells, are extremely adaptable and, when extracted from a brain, cultured and then re-injected in a lesioned area of the same brain, they can help repair and rebuild it. The treatment using them would take some time to be available for general public use, as it has to clear regulations and trials.

History
Historical progression of spasticity and the upper motor neuron lesion on which it is based has progressed considerably in recent decades. However, the term "spasticity" is still often used interchangeably with "upper motor neuron syndrome" in the clinical settings, and it is not unusual to see patients labeled as "spastic" who actually demonstrate not just spasticity alone, but also an array of upper motor neuron findings.Research has clearly shown that exercise is beneficial for spastic muscles, even though in the very early days of research it was assumed that strength exercise would increase spasticity. Also, from at least the 1950s through at least the 1980s, there was a strong focus on other interventions for spastic muscles, particularly stretching and splinting, but the evidence does not support these as effective. While splinting is not considered effective for decreasing spasticity, a range of different orthotics are effectively used for preventing muscle contractures on patients with spasticity. In the case of spastic diplegia there is also a permanent neurosurgical treatment for spasticity, selective dorsal rhizotomy, that directly targets nerves in the spine that cause the spasticity, and destroys them, so that the spasticity cannot be activated at all.

See also
References
Further reading
Lance JW: Symposium synopsis, in Feldman RG, Young RR, Koella WP (eds): Spasticity: Disordered Motor Control. Chicago, Yearbook Medical Publishers, 1980
"Other Complications of Spinal Cord Injury: Spasticity." (Louis Calder Memorial Library of the University of Miami/Jackson Memorial Medical Center, October 3, 2002), http://calder.med.miami.edu/pointis/spasticity.html
Maureen E. Neistadt; Elizabeth Blesedell Crepeau, eds. (1998). Willard and Spackmans occupational therapy. Philadelphia: Lippincott-Raven Publishers. pp. 233. ISBN 978-0-397-55192-7.
This article contains text from the public domain document at http://www.ninds.nih.gov/health_and_medical/disorders/spasticity_doc.htm
Douglas, Wallace M.; Bruce H Ross; Christine K. Thomas (Aug 25, 2005). "Motor unit behaviour during clonus". Journal of Applied Physiology. 99 (6): 2166–2172. CiteSeerX 10.1.1.501.9581 </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 Standing and can you explain it in depth? [/INST] Standing, also referred to as orthostasis, is a position in which the body is held in an erect ("orthostatic") position and supported only by the feet.  Although seemingly static, the body rocks slightly back and forth from the ankle in the sagittal plane. The sagittal plane bisects the body into right and left sides. The sway of quiet standing is often likened to the motion of an inverted pendulum.Standing at attention is a military standing posture, as is stand at ease, but these terms are also used in military-style organisations and in some professions which involve standing, such as modeling. At ease refers to the classic military position of standing with legs slightly apart, not in as formal or regimented a pose as standing at attention. In modeling, model at ease refers to the model standing with one leg straight, with the majority of the weight on it, and the other leg tucked over and slightly around.

Control
Standing posture relies on dynamic rather than static balance. The human center of mass is in front of the ankle, and unlike in tetrapods, the base of support is narrow, consisting of only two feet. A static pose would cause humans to fall forward onto the face. In addition, there are constant external perturbations, such as breezes, and internal perturbations that come from respiration. Erect posture requires adjustment and correction. There are many mechanisms in the body that are suggested to control this, e.g. a spring action in muscles, higher control from the nervous system or core muscles.  Humans begin to stand between 8 and 12 months of age.

Spring action
Traditionally, such correction was explained by the spring action of the muscles, a local mechanism taking place without the intervention of the central nervous system (C.N.S.). Recent studies, however, show that this spring action by itself is insufficient to prevent a forward fall. Also, human sway is too complicated to be adequately explained by spring action.

Nervous system
According to current theory, the nervous system continually and unconsciously monitors our direction and velocity. The vertical body axis alternates between tilting forward and backward. Before each tilt reaches the tipover point the nervous system counters with a signal to reverse direction. Sway also occurs in the hip and there is a slight winding and unwinding of the lower back.An analogy would be a ball that volleys back and forth between two players without touching the ground. The muscle exertion required to maintain an aligned standing posture is crucial but minimal. Electromyography has detected slight activity in the muscles of the calves, hips and lower back.

Core muscles
The core muscles play a role in maintaining stability. The core muscles are deep muscle layers that lie close to the spine and provide structural support. The transverse abdominals wrap around the spine and function as a compression corset. The multifidi are intersegmental muscles. Dysfunction in the core muscles has been implicated in back pain.

Expansion of pendulum model
Some investigators have replaced the ankle inverted pendulum analogy with a model of double linked pendulums involving both hip and ankle sway. Neither model is accepted as more than an approximation. Analysis of postural sway shows much more variation than is seen in a physical pendulum or even a pair of coupled pendulums. Furthermore, quiet standing involves activity in all joints, not just the ankles or hips.In the past the variation was attributed to random effects. A more recent interpretation is that sway has a fractal structure. A fractal pattern consists of a motif repeated at varying levels of magnification. The levels are related by a ratio called the fractal dimension. It is believed that the fractal pattern offers a range of fine and gross control tuning. Fractal dimension is altered in some motor dysfunctions. In other words, the body cannot compensate well enough for imbalances.

Pathology
Although standing per se is not dangerous, there are pathologies associated with it. One short term condition is orthostatic hypotension, and long term conditions are sore feet, stiff legs and low back pain.

Orthostatic hypotension
Orthostatic hypotension is characterized by an unusually low blood pressure when the patient is standing up.
It can cause dizziness, lightheadedness, headache, blurred or dimmed vision and fainting, because the brain does not get sufficient blood supply. This, in turn, is caused by gravity, pulling the blood into the lower part of the body.
Normally, the body compensates, but in the presence of other factors, e.g </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 Pituitary apoplexy and can you explain it in depth? [/INST] Pituitary apoplexy is bleeding into or impaired blood supply of the pituitary gland. This usually occurs in the presence of a tumor of the pituitary, although in 80% of cases this has not been diagnosed previously. The most common initial symptom is a sudden headache, often associated with a rapidly worsening visual field defect or double vision caused by compression of nerves surrounding the gland. This is often followed by acute symptoms caused by lack of secretion of essential hormones, predominantly adrenal insufficiency.The diagnosis is achieved with magnetic resonance imaging and blood tests. Treatment is by the timely correction of hormone deficiencies. In many cases, surgical decompression is required. Many people who have had a pituitary apoplexy develop pituitary hormone deficiencies and require long-term hormone supplementation. The first case of the disease was recorded in 1898.

Signs and symptoms
Acute symptoms
The initial symptoms of pituitary apoplexy are related to the increased pressure in and around the pituitary gland. The most common symptom, in over 95% of cases, is a sudden-onset headache located behind the eyes or around the temples. It is often associated with nausea and vomiting. Occasionally, the presence of blood leads to irritation of the lining of the brain, which may cause neck rigidity and intolerance to bright light, as well as a decreased level of consciousness. This occurs in 24% of cases.

Pressure on the part of the optic nerve known as the chiasm, which is located above the gland, leads to loss of vision on the outer side of the visual field on both sides, as this corresponds to areas on the retinas supplied by these parts of the optic nerve; it is encountered in 75% of cases. Visual acuity is reduced in half, and over 60% have a visual field defect. The visual loss depends on which part of the nerve is affected. If the part of the nerve between the eye and the chiasm is compressed, the result is vision loss in one eye. If the part after the chiasm is affected, visual loss on one side of the visual field occurs.Adjacent to the pituitary lies a part of the skull base known as the cavernous sinus. This contains a number of nerves that control the eye muscles. 70% of people with pituitary apoplexy experience double vision due to compression of one of the nerves. In half of these cases, the oculomotor nerve (the third cranial nerve), which controls a number of eye muscles, is affected. This leads to diagonal double vision and a dilated pupil. The fourth (trochlear) and sixth (abducens) cranial nerves are located in the same compartment and can cause diagonal or horizontal double vision, respectively. The oculomotor nerve is predominantly affected as it lies closest to the pituitary. The cavernous sinus also contains the carotid artery, which supplies blood to the brain; occasionally, compression of the artery can lead to one-sided weakness and other symptoms of stroke.

Endocrine dysfunction
The pituitary gland consists of two parts, the anterior (front) and posterior (back) pituitary. Both parts release hormones that control numerous other organs. In pituitary apoplexy, the main initial problem is a lack of secretion of adrenocorticotropic hormone (ACTH, corticotropin), which stimulates the secretion of cortisol by the adrenal gland. This occurs in 70% of those with pituitary apoplexy. A sudden lack of cortisol in the body leads to a constellation of symptoms called "adrenal crisis" or "Addisonian crisis" (after a complication of Addisons disease, the main cause of adrenal dysfunction and low cortisol levels). The main problems are low blood pressure (particularly on standing), low blood sugars (which can lead to coma) and abdominal pain; the low blood pressure can be life-threatening and requires immediate medical attention.Hyponatremia, an unusually low level of sodium in the blood that may cause confusion and seizures, is found in 40% of cases. This may be caused by low cortisol levels or by inappropriate release of antidiuretic hormone (ADH) from the posterior pituitary. Several other hormonal deficiencies may develop in the subacute phase. 50% have a deficiency in thyroid-stimulating hormone (TSH), leading to hyposecretion of thyroid hormone by the thyroid gland and characteristic symptoms such as fatigue, weight gain, and cold intolerance. 75% develop a deficiency to gonadotropins (LH and FSH), which control the reproductive hormone glands. This leads to a disrupted menstrual cycle, infertility, and decreased libido.

Causes
Almost all cases of pituitary apoplexy arise from a pituitary adenoma, a benign tumor of the pituitary gland. In 80%, the patient has been previously unaware of this (although some will retrospectively report associated symptoms). It was previously thought that particular types of pituitary tumors were more prone to apoplexy than others, but this has not been confirmed. In absolute terms, only a very small proportion of pituitary tumors eventually undergoes apoplexy. In an analysis of incidentally found pituitary tumors, apoplexy occurred in 0.2% annually, but the risk was higher in tumors larger than 10 mm ("macroadenomas") and tumors that were growing more rapidly; in a meta-analysis, not all these associations achieved statistical significance.The majority of cases (60–80%) are not precipitated by a particular cause. A quarter has a history of high blood pressure, but this is a common problem in the general population, and it is not clear whether it significantly increase the risk of apoplexy. A number of cases has been reported in association with particular conditions and situations; it is uncertain whether these were in fact causative. Amongst reported associations are surgery (especially coronary artery bypass graft, where there are significant fluctuations in the blood pressure), disturbances in blood coagulation or medication that inhibits coagulation, radiation therapy to the pituitary, traumatic brain injury, pregnancy (during which the pituitary enlarges) and treatment with estrogens. Hormonal stimulation tests of the pituitary have been reported to provoke episodes. Treatment of prolactinomas (pituitary adenomas that secrete prolactin) with dopamine agonist drugs, as well as withdrawal of such treatment, has been reported to precipitate apoplexy.Hemorrhage from a Rathkes cleft cyst, a remnant of Rathkes pouch that normally regresses after embryological development, may cause symptoms that are indistinguishable from pituitary apoplexy. Pituitary apoplexy is regarded by some as distinct from Sheehans syndrome, where the pituitary undergoes infarction as a result of prolonged very low blood pressure, particularly when caused by bleeding after childbirth. This condition usually occurs in the absence of a tumor. Others regard Sheehans syndrome as a form of pituitary apoplexy.

Mechanism
The pituitary gland is located in a recess in the skull base known as the sella turcica ("Turkish saddle", after its shape). It is attached to the hypothalamus, a part of the brain, by a stalk that also contains the blood vessels that supply the gland. It is unclear why pituitary tumors are five times more likely to bleed than other tumors in the brain. There are various proposed mechanisms by which a tumor can increase the risk of either infarction (insufficient blood supply leading to tissue dysfunction) or hemorrhage. The pituitary gland normally derives its blood supply from vessels that pass through the hypothalamus, but tumors develop a blood supply from the nearby inferior hypophyseal artery that generates a higher blood pressure, possibly accounting for the risk of bleeding. Tumors may also be more sensitive to fluctuations in blood pressure, and the blood vessels may show structural abnormalities that make them vulnerable to damage. It has been suggested that infarction alone causes milder symptoms than either hemorrhage or hemorrhagic infarction (infarction followed by hemorrhage into the damaged tissue). Larger tumors are more prone to bleeding, and more rapidly growing lesions (as evidenced by detection of increased levels of the protein PCNA) may also be at a higher risk of apoplexy.After an apoplexy, the pressure inside the sella turcica rises, and surrounding structures such as the optic nerve and the contents of the cavernous sinus are compressed. The raised pressure further impairs the blood supply to the pituitary hormone-producing tissue, leading to tissue death due to insufficient blood supply.

Diagnosis
It is recommended that magnetic resonance imaging (MRI) scan of the pituitary gland is performed if the diagnosis is suspected; this has a sensitivity of over 90% for detecting pituitary apoplexy; it may demonstrate infarction (tissue damage due to a decreased blood supply) or hemorrhage. Different MRI sequences can be used to establish when the apoplexy occurred, and the predominant form of damage (hemorrhage or infarction). If MRI is not suitable (e.g. due to claustrophobia or the presence of metal-containing implants), a computed tomography (CT) scan may demonstrate abnormalities in the pituitary gland, although it is less reliable. Many pituitary tumors (25%) are found to have areas of hemorrhagic infarction on MRI scans, but apoplexy is not said to exist unless it is accompanied by symptoms.In some instances, lumbar puncture may be required if there is a suspicion that the symptoms might be caused by other problems (meningitis or subarachnoid hemorrhage). This is the examination of the cerebrospinal fluid that envelops the brain and the spinal cord; the sample is obtained with a needle that is passed under local anesthetic into the spine. In pituitary apoplexy the results are typically normal, although abnormalities may be detected if blood from the pituitary has entered the subarachnoid space. If there is remaining doubt about the possibility of subarachnoid hemorrhage (SAH), a magnetic resonance angiogram (MRI with a contrast agent) may be required to identify aneurysms of the brain blood vessels, the most common cause of SAH.Professional guidelines recommend that if pituitary apoplexy is suspected or confirmed, the minimal blood tests performed should include a complete blood count, urea (a measure of renal function, usually performed together with creatinine), electrolytes (sodium and potassium), liver function tests, routine coagulation testing, and a hormonal panel including IGF-1, growth hormone, prolactin,  luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, thyroid hormone, and either testosterone in men or estradiol in women.Visual field testing is recommended as soon as possible after diagnosis, as it quantifies the severity of any optic nerve involvement, and may be required to decide on surgical treatment.

Treatment
The first priority in suspected or confirmed pituitary apoplexy is stabilization of the circulatory system. Cortisol deficiency can cause severe low blood pressure. Depending on the severity of the illness, admission to a high dependency unit (HDU) may be required.Treatment for acute adrenal insufficiency requires the administration of intravenous saline or dextrose solution; volumes of over two liters may be required in an adult. This is followed by the administration of hydrocortisone, which is pharmaceutical grade cortisol, intravenously or into a muscle. The drug dexamethasone has similar properties, but its use is not recommended unless it is required to reduce swelling in the brain around the area of hemorrhage. Some are well enough not to require immediate cortisol replacement; in this case, blood levels of cortisol are determined at 9:00 AM (as cortisol levels vary over the day). A level below 550 nmol/l indicates a need for replacement.The decision on whether to surgically decompress the pituitary gland is complex and mainly dependent on the severity of visual loss and visual field defects. If visual acuity is severely reduced, there are large or worsening visual field defects, or the level of consciousness falls consistently, professional guidelines recommend that surgery is performed. Most commonly, operations on the pituitary gland are performed through transsphenoidal surgery. In this procedure, surgical instruments are passed through the nose towards the sphenoid bone, which is opened to give access to the cavity that contains the pituitary gland. Surgery is most likely to improve vision if there was some remaining vision before surgery, and if surgery is undertaken within a week of the onset of symptoms.Those with relatively mild visual field loss or double vision only may be managed conservatively, with close observation of the level of consciousness, visual fields, and results of routine blood tests. If there is any deterioration, or expected spontaneous improvement does not occur, surgical intervention may still be indicated. If the apoplexy occurred in a prolactin-secreting tumor, this may respond to dopamine agonist treatment.After recovery, people who have had pituitary apoplexy require follow-up by an endocrinologist to monitor for long-term consequences. MRI scans are performed 3–6 months after the initial episode and subsequently on an annual basis. If after surgery some tumor tissue remains, this may respond to medication, further surgery, or radiation therapy with a "gamma knife".

Prognosis
In larger case series, the mortality was 1.6% overall. In the group of patients who were unwell enough to require surgery, the mortality was 1.9%, with no deaths in those who could be treated conservatively.After an episode of pituitary apoplexy, 80% of people develop hypopituitarism and require some form of hormone replacement therapy. The most common problem is growth hormone deficiency, which is often left untreated but may cause decreased muscle mass and strength, obesity and fatigue. 60–80% require hydrocortisone replacement (either permanently or when unwell), 50–60% need thyroid hormone replacement, and 60–80% of men require testosterone supplements </s>