<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 Rolandic epilepsy and can you explain it in depth? [/INST] Benign Rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes (BCECTS) is the most common epilepsy syndrome in childhood. Most children will outgrow the syndrome (it starts around the age of 3–13 with a peak around 8–9 years and stops around age 14–18), hence the label benign. The seizures, sometimes referred to as sylvian seizures, start around the central sulcus of the brain (also called the centrotemporal area, located around the Rolandic fissure, after Luigi Rolando).

Signs and symptoms
The cardinal features of Rolandic epilepsy are infrequent, often single, focal seizures consisting of:
a. unilateral facial sensorimotor symptoms (30% of patients)
b. oropharyngolaryngeal manifestations (53% of patients)
c. speech arrest (40% of patients), and
d. hypersalivation (30% of patients)Hemifacial sensorimotor seizures are often entirely localised in the lower lip or spread to the ipsilateral hand. Motor manifestations are sudden, continuous or bursts of clonic contractions, usually lasting from a few seconds to a minute. Ipsilateral tonic deviation of the mouth is also common. Hemifacial sensory symptoms consist of unilateral numbness mainly in the corner of the mouth.
Hemifacial seizures are often associated with an inability to speak and hypersalivation:
The left side of my mouth felt numb and started jerking and pulling to the left, and I could not speak to say what was happening to me.
Negative myoclonus can be observed in some cases, as an interruption of tonic muscular activity
Oropharyngolaryngeal ictal manifestations are unilateral sensorimotor symptoms inside the mouth. Numbness, and more commonly paraesthesias (tingling, prickling, freezing), are usually diffuse on one side or, exceptionally, may be highly localised even to one tooth. Motor oropharyngolaryngeal symptoms produce strange sounds, such as death rattle, gargling, grunting and guttural sounds, and combinations:
In his sleep, he was making guttural noises, with his mouth pulled to the right, ‘as if he was chewing his tongue’. We heard her making strange noises ‘like roaring’ and found her unresponsive, head raised from the pillow, eyes wide open, rivers of saliva coming out of her mouth, rigid.
Arrest of speech is a form of anarthria. The child is unable to utter a single intelligible word and attempts to communicate with gestures.
My mouth opened and I could not speak. I wanted to say I cannot speak. At the same time, it was as if somebody was strangling me.
Hypersalivation, a prominent autonomic manifestation, is often associated with hemifacial seizures, oro-pharyngo-laryngeal symptoms and speech arrest. Hypersalivation is not just frothing:
Suddenly my mouth is full of saliva, it runs out like a river and I cannot speak.
Syncope-like epileptic seizures may occur, probably as a concurrent symptom of Panayiotopoulos syndrome:
She lies there, unconscious with no movements, no convulsions, like a wax work, no life.
Consciousness and recollection are fully retained in more than half (58%) of Rolandic seizures.
I felt that air was forced into my mouth, I could not speak and I could not close my mouth. I could understand well everything said to me. Other times I feel that there is food in my mouth and there is also a lot of salivation. I cannot speak.
In the remainder (42%), consciousness becomes impaired during the ictal progress and in one third there is no recollection of ictal events.
Progression to hemiconvulsions or generalised tonic-clonic seizures occurs in around half of children and hemiconvulsions may be followed by postictal Todds hemiparesis.
Duration and circadian distribution: Rolandic seizures are usually brief, lasting for 1–3 minutes. Three-quarters of seizures occur during nonrapid eye movement sleep, mainly at sleep onset or just before awakening.
Status epilepticus: Although rare, focal motor status or hemiconvulsive status epilepticus is more likely to occur than secondarily generalised convulsive status epilepticus, which is exceptional. Opercular status epilepticus usually occurs in children with atypical evolution or may be induced by carbamazepine or lamotrigine. This state lasts for hours to months and consists of ongoing unilateral or bilateral contractions of the mouth, tongue or eyelids, positive or negative subtle perioral or other myoclonus, dysarthria, speech arrest, difficulties in swallowing, buccofacial apraxia and hypersalivation. These are often associated with continuous spikes and waves on an EEG during NREM sleep.
Other seizure types: Despite prominent hypersalivation, focal seizures with primarily autonomic manifestations (autonomic seizures) are not considered part of the core clinical syndrome of Rolandic epilepsy.  However, some children may present with independent autonomic seizures or seizures with mixed Rolandic-autonomic manifestations including emesis as in Panayiotopoulos syndrome.Atypical forms:  Rolandic epilepsy may present with atypical manifestations such early age at onset, developmental delay or learning difficulties at inclusion, other seizure types, atypical EEG abnormalities.These children usually have normal intelligence and development. Learning can remain unimpaired while a child is afflicted with Rolandic epilepsy.

Cause
Benign epilepsy with centrotemporal spikes is thought to be a genetic disorder. An autosomal dominant inheritance with age dependency and variable penetrance has been reported, although not all studies support this theory. Linkage studies have pointed to a possible susceptibility region on chromosome 15q14, in the vicinity of the alpha-7 subunit of the acetylcholine receptor. Most studies show a slight male predominance. Because of the benign course and age-specific occurrence, it is thought to represent a hereditary impairment of brain maturation.An association with ELP4 has been identified.

Diagnosis
The diagnosis can be confirmed when the characteristic centrotemporal spikes are seen on electroencephalography (EEG). Typically, high-voltage spikes followed by slow waves are seen. Given the nocturnal activity, a sleep EEG can often be helpful. Technically, the label "benign" can only be confirmed if the childs development continues to be normal during follow-up </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 Horizontal gaze palsy 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 Meiges syndrome and can you explain it in depth? [/INST] Meiges syndrome is a type of dystonia. It is also known as Brueghels syndrome and oral facial dystonia. It is actually a combination of two forms of dystonia, blepharospasm and oromandibular dystonia (OMD).
When OMD is combined with blepharospasm, it may be referred to as Meiges Syndrome named after Henri Meige, the French neurologist who first described the symptoms in detail in 1910. The symptoms usually begin between the ages of 30 and 70 years old and appear to be more common in women than in men (2:1 ratio). The combination of upper and lower dystonia is sometimes called cranial-cervical dystonia. The incidence is about one case in 20,000 people.

Presentation
The main symptoms involve involuntary blinking and chin thrusting. Some patients may experience excessive tongue protrusion, squinting, light sensitivity, muddled speech, or uncontrollable contraction of the platysma muscle.  Some Meiges patients also have "laryngeal dystonia" (spasms of the larynx). Blepharospasm may lead to embarrassment in social situations, and oromandibular dystonia can affect speech, making it difficult to carry on the simplest conversations. This can cause difficulty in both personal and professional contexts, and in some cases may cause patients to withdraw from social situations.The condition tends to affect women more frequently than men.

Symptoms
Oromandibular Symptoms

difficulty opening the mouth (trismus)
clenching or grinding of the teeth (bruxism)
spasms of jaw opening
sideways deviation or protrusion of the jaw
lip tightening and pursing
drawing back (retraction) of the corners of the mouth
deviation or protrusion of the tongue.
jaw pain
difficulties eating and drinking
difficulties speaking (dysarthria)Blepharospasm symptoms

the first symptom to appear is an increased rate of blinking
uncontrollable squinting/closing of eyes
light sensitivity (photophobia)
squinting/eyes closing during speech
uncontrollable eyes closing shut (rare instances completely causing blindness)In addition, in some patients, the dystonic spasms may sometimes be provoked by certain activities, such as talking, chewing, or biting. Particular activities or sensory tricks may sometimes temporarily alleviate OMD symptoms, including chewing gum, talking, placing a toothpick in the mouth, lightly touching the lips or chin, or applying pressure beneath the chin.

Diagnosis
Meiges is commonly misdiagnosed and most doctors will not be familiar with this condition due to its rare incidence. Usually, a neurologist specializing in psychomotor disorders can detect Meiges. There are currently no technological diagnostic tools to detect Meiges, as it cannot be identified using blood chemistry analysis or radiological imaging, such as MRI or CT scans. A patient presenting with signs of OMD alone may be misdiagnosed with TMJD.Patients with idiopathic Meiges syndrome do not quickly respond to anticholinergic drug treatments, a diagnostic sign that can help differentiate it from acute dystonia, which does respond to anticholinergic drugs.

Upper and lower dystonia types
The Greek word blepharon means "eyelid". Spasm means "uncontrolled muscle contraction". The term blepharospasm [blef-a-ro-spaz-m] can be applied to any abnormal blinking or eyelid tic or twitch resulting from any cause, ranging from dry eyes to Tourettes syndrome to tardive dyskinesia. The blepharospasm referred to here is officially called benign essential blepharospasm (BEB) to distinguish it from the less serious secondary blinking disorders. "Benign" indicates the condition is not life-threatening, and "essential" is a medical term meaning "of unknown cause". It is both a cranial and a focal dystonia. Cranial refers to the head and focal indicates confinement to one part. The word dystonia describes abnormal involuntary sustained muscle contractions and spasms. Patients with blepharospasm have normal eyes. The visual disturbance is due solely to the forced closure of the eyelids.Oromandibular dystonia (OMD) is a form of focal dystonia that affects varying areas of the head and neck including the lower face, jaw, tongue and larynx.  The spasms may cause the mouth to pull open, shut tight, or move repetitively.  Speech and swallowing may be distorted.  It is often associated with dystonia of the cervical muscles (Spasmodic Torticollis), eyelids (Blepharospasm), or larynx (Spasmodic Dysphonia).In patients with OMD, involuntary contractions may involve the muscles used for chewing (masticatory muscles). These may include the thick muscle in the cheek that closes the jaw (masseter muscle) and the broad muscle that draws back the lower jaw and closes the mouth (temporalis muscle). Some patients may also experience involuntary contractions of the wide muscle at the side of the neck (platysmal muscle). This muscle draws down the corner of the mouth and lower lip or other muscle groups.

Treatment
In some cases Meiges syndrome can be reversed when it is caused by medication. Botulinum toxin injections can be helpful for the blepharospasm and for masseter spasm.

See also
Mogigraphia

References

Paulson, George W </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 Mastitis and can you explain it in depth? [/INST] Mastitis is inflammation of the breast or udder, usually associated with breastfeeding. Symptoms typically include local pain and redness. There is often an associated fever and general soreness. Onset is typically fairly rapid and usually occurs within the first few months of delivery. Complications can include abscess formation.Risk factors include poor latch, cracked nipples, use of a breast pump, and weaning. The bacteria most commonly involved are Staphylococcus and Streptococci. Diagnosis is typically based on symptoms. Ultrasound may be useful for detecting a potential abscess.Prevention is by proper breastfeeding techniques. When infection is present, antibiotics such as cephalexin may be recommended. Breastfeeding should typically be continued, as emptying the breast is important for healing. Tentative evidence supports benefits from probiotics. About 10% of breastfeeding women are affected.

Types
When it occurs in breastfeeding mothers, it is known as puerperal mastitis, lactation mastitis, or lactational mastitis. When it occurs in non breastfeeding women it is known as non-puerperal or nonlactational. Mastitis can, in rare cases, occur in men. Inflammatory breast cancer has symptoms very similar to mastitis and must be ruled out.
The symptoms are similar for puerperal and nonpuerperal mastitis but predisposing factors and treatment can be very different.

Pregnancy related
Puerperal mastitis is the inflammation of the breast in connection with pregnancy, breastfeeding or weaning. Since one of the most prominent symptoms is tension and engorgement of the breast, it is thought to be caused by blocked milk ducts or milk excess. It is relatively common; estimates range depending on methodology between 5–33%. However, only about 0.4–0.5% of breastfeeding mothers develop an abscess.Some predisposing factors are known but their predictive value is minimal. It appears that proper breastfeeding technique, frequent breastfeeding and avoidance of stress are the most important factors that can be influenced.
Light cases of mastitis are often called breast engorgement; the distinction is overlapping and possibly arbitrary or subject to regional variations.

Non pregnancy related
The term nonpuerperal mastitis describes inflammatory lesions of the breast occurring unrelated to pregnancy and breastfeeding. This article includes description of mastitis as well as various kinds of mammary abscesses. Skin related conditions like dermatitis and foliculitis are a separate entity.
Names for non-puerperal mastitis are not used very consistently and include mastitis, subareolar abscess, duct ectasia, periductal inflammation, Zuskas disease and others.
Periductal mastitis is a form of nonlactational mastitis, and is characterized by inflammation of the subareolar ducts. Although the cause of periductal mastitis is currently unknown, it is predicted that smoking may be related. This condition is mainly seen in young women but can also be seen in men.

Signs and symptoms
Lactation mastitis usually affects only one breast and the symptoms can develop quickly. It develops into three stages, from the initial stage, the pus formation stage, to the restoration stage. The signs and symptoms usually appear suddenly and they include:

Breast tenderness or warmth to the touch
General malaise or feeling ill
Swelling of the breast
Pain or a burning sensation continuously or while breast-feeding
Skin redness, often in a wedge-shaped pattern
Fever of 101 F (38.3 C) or greater
The affected breast can then start to appear lumpy and red.Some women may also experience flu-like symptoms such as:

Aches
Shivering and chills
Feeling anxious or stressed
FatigueContact should be made with a health care provider with special breastfeeding competence as soon as the patient recognizes the combination of signs and symptoms. Most of the women first experience the flu-like symptoms and just after they may notice a sore red area on the breast. Also, women should seek medical care if they notice any abnormal discharge from the nipples, if  breast pain is making it difficult to function each day, or they have prolonged, unexplained breast pain.

Breast abscess
A breast abscess is a collection of pus that develops in the breast with various causes. During lactation, breast abscess develops only rarely, most sources cite about 0.4–0.5% of breastfeeding women. Known risk factors are age over 30, primiparous and late delivery. No correlation was found with smoking status; however, this may be in part because far fewer smoking women choose to breastfeed. Antibiotics were not shown effective in prevention of lactation abscess but are useful to treat a secondary infection (see the section on the treatment of breast abscess in this article).
Keratinizing squamous metaplasia of lactiferous ducts may play a similar role in the pathogenesis of nonpuerperal subareolar abscess.

Causes
Since the 1980s mastitis has often been divided into non-infectious and infectious sub-groups. However, recent research  suggests that it may not be feasible to make divisions in this way. It has been shown that types and amounts of potentially pathogenic bacteria in breast milk are not correlated to the severity of symptoms. Moreover, although only 15% of women with mastitis in Kvist et al.s study were given antibiotics, all recovered and few had recurring symptoms. Many healthy breastfeeding women wishing to donate breast milk have potentially pathogenic bacteria in their milk but have no symptoms of mastitis.

Risk factors
Mastitis typically develops when the milk is not properly removed from the breast. Milk stasis can lead to the milk ducts in the breasts becoming blocked, as the breast milk is not being properly and regularly expressed. It has also been suggested that blocked milk ducts can occur as a result of pressure on the breast, such as tight-fitting clothing or an over-restrictive bra, although there is sparse evidence for this supposition.
Mastitis may  occur when the baby is not appropriately attached to the breast while feeding, when the baby has infrequent feeds or has problems suckling the milk out of the breast.
The presence of cracks or sores on the nipples increases the likelihood of infection. Tight clothing or ill-fitting bras may also cause problems as they compress the breasts.  There is a possibility that infants carrying infectious pathogens in their noses can infect their mothers; the clinical significance of this finding is still unknown.
Mastitis and breast abscesses can also be caused by direct trauma to the breast. Such injury can occur for example during sports activities or due to seat belt injury.
Mastitis can also develop due to contamination of a breast implant or any other foreign body, for example after nipple piercing. In such cases, the removal of the foreign body is indicated.Women who are breastfeeding are at risk for developing mastitis especially if they have sore or cracked nipples or have had mastitis before while breastfeeding another baby. Also, the chances of getting mastitis increases if women use only one position to breastfeed or wear a tight-fitting bra, which may restrict milk flow  Difficulties in getting a nursing infant to latch on to the breast can also increase the risk for mastitis.Women with diabetes, chronic illness, AIDS, or an impaired immune system may be more susceptible to the development of mastitis.

Infection
Some women (approximately 15%) will require antibiotic treatment for infection which is usually caused by bacteria from the skin or the babys mouth entering the milk ducts through skin lesions of the nipple or through the opening of the nipple. Infection is usually caused by Staphylococcus aureus. Infectious pathogens commonly associated with mastitis are Staphylococcus aureus, Streptococcus spp. and Gram-negative bacilli such as Escherichia coli. Salmonella spp., mycobacteria, and fungi such as Candida and Cryptococcus have been identified in rare instances.Recent research suggests that infectious pathogens play a much smaller role in the pathogenesis than was commonly assumed only a few years ago. Most detected pathogens are very common species that are natural part of the breast fauna and simple detection of their presence is not sufficient to prove a causative role. Furthermore, there are indications that treatment with antibiotics may have minimal impact, and over-all there is insufficient evidence to confirm or refute the effectiveness of antibiotic therapy for treating lactational mastitis.

Diagnosis
The diagnosis of mastitis and breast abscess can usually be made based on a physical examination. The doctor will also take into account the signs and symptoms of the condition.
However, if the doctor is not sure whether the mass is an abscess or a tumor, a breast ultrasound may be performed. The ultrasound provides a clear image of the breast tissue and may be helpful in distinguishing between simple mastitis and abscess or in diagnosing an abscess deep in the breast. The test consists of placing an ultrasound probe over the breast.
In cases of infectious mastitis, cultures may be needed in order to determine what type of organism is causing the infection. Cultures are helpful in deciding the specific type of antibiotics that will be used in curing the disease. These cultures may be taken either from the breast milk or of the material aspirated from an abscess.
Mammograms or breast biopsies are normally performed on women who do not respond to treatment or on non-breastfeeding women. This type of tests is sometimes ordered to exclude the possibility of a rare type of breast cancer which causes symptoms similar to those of mastitis.

Differential diagnosis
Breast cancer may coincide with or mimic symptoms of mastitis. Only full resolution of symptoms and careful examination are sufficient to exclude the diagnosis of breast cancer.
Lifetime risk for breast cancer is significantly reduced for women who were pregnant and breastfeeding. Mastitis episodes do not appear to influence lifetime risk of breast cancer.
Mastitis does however cause great difficulties in diagnosis of breast cancer and delayed diagnosis and treatment can result in worse outcome.
Breast cancer may coincide with mastitis or develop shortly afterwards. All suspicious symptoms that do not completely disappear within 5 weeks must be investigated.
Breast cancer incidence during pregnancy and lactation is assumed to be the same as in controls. Course and prognosis are also very similar to age matched controls. However diagnosis during lactation is particularly problematic, often leading to delayed diagnosis and treatment.
Some data suggest that noninflammatory breast cancer incidence is increased within a year following episodes of nonpuerperal mastitis and special care is required for follow-up cancer prevention screening. So far only data from short term observation is available and total risk increase can not be judged. Because of the very short time between presentation of mastitis and breast cancer in this study it is considered very unlikely that the inflammation had any substantial role in carcinogenesis, rather it would appear that some precancerous lesions may increase the risk of inflammation (hyperplasia causing duct obstruction, hypersensitivity to cytokines or hormones) or the lesions may have common predisposing factors.
A very serious type of breast cancer called inflammatory breast cancer presents with similar symptoms as mastitis (both puerperal and nonpuerperal). It is the most aggressive type of breast cancer with the highest mortality rate. The inflammatory phenotype of IBC is thought to be mostly caused by invasion and blocking of dermal lymphatics, however it was recently shown that NF-κB target genes activation may significantly contribute to the inflammatory phenotype. Case reports show that inflammatory breast cancer symptoms can flare up following injury or inflammation making it even more likely to be mistaken for mastitis. Symptoms are also known to partially respond to progesterone and antibiotics, reaction to other common medications can not be ruled out at this point.

Treatment
In lactation mastitis, frequent emptying of both breasts by breastfeeding is essential. Also essential is adequate fluid supply for the mother and baby.
For breastfeeding women with light mastitis, massage and application of heat prior to feeding can help as this may aid unblocking the ducts. However, in more severe cases of mastitis heat or massage could make the symptoms worse and cold compresses are better suited to contain the inflammation.
Nonpuerperal mastitis is treated by medication and possibly aspiration or drainage (see in particular treatment of subareolar abscess and treatment of granulomatous mastitis). According to a BMJ best practice report, antibiotics are generally to be used in all nonpuerperal mastitis cases, with replacement of the antibiotics by an antifungal agent such as fluconazole in cases of deep fungal infections, and corticosteroids are to be used in case of granulomatous mastitis (with differential diagnosis to tuberculosis infection of the breast).In idiopathic granulomatous mastitis, successful treatment includes invasive surgical procedures or less invasive treatment with steroid medications.

Antibiotics
In lactational mastitis, antibiotics are not needed in the overwhelming majority of cases and should be used only for bacterial infections. For people with nonsevere infections, dicloxacillin or cephalexin are recommended. For people with severe infections, vancomycin is recommended. The length of antibiotic treatment ranges anywhere from 5–14 days. The effects of antibiotics has not been well studied as of 2013.

Breast abscess
An abscess (or suspected abscess) in the breast may be treated by ultrasound-guided fine-needle aspiration (percutaneous aspiration) or by surgical incision and drainage; each of these approaches is performed under antibiotic coverage. In case of puerperal breast abscess, breastfeeding from the affected breast should be continued where possible.For small breast abscesses, ultrasound-guided fine needle aspiration such as to completely drain the abscess is widely recognized as a preferred initial management.One recommended treatment includes antibiotics, ultrasound evaluation and, if fluid is present, ultrasound-guided fine needle aspiration of the abscess with an 18 gauge needle, under saline lavage until clear. The exudate is then sent for microbiological analysis for identification of the pathogen and determination of its antibiotic sensitivity profile, which may in turn give an indication for changing the antibiotics. At follow-up, a mammography is performed if the condition has resolved; otherwise the ultrasound-guided fine-needle aspiration with lavage and microbiological analysis is repeated. If three to five aspirations still do not resolve the condition, percutaneous drainage in combination with placement of an indwelling catheter is indicated, and only if several attempts at ultrasound-guided drainage fail, surgical resection of the inflamed lactiferous ducts (preferably performed after the acute episode is over). It is noted, however, that even the excision of the affected ducts does not necessarily prevent recurrence.Nonpuerperal breast abscesses have a higher rate of recurrence compared to puerperal breast abscesses. There is a high statistical correlation of nonpuerperal breast abscess with diabetes mellitus (DM). On this basis, it has recently been suggested that diabetes screening should be performed on patients with such abscess.Although there are a number of recommendations regarding the treatment of breast abscesses, a 2015 review found insufficient evidence of whether needle aspiration is comparable to incision and drainage, or whether antibiotics should generally be given to women undergoing incision and drainage.

Prognosis
Temperature and severity of symptoms at presentation do not predict outcome; women with sore or damaged nipples may need special attention.

Epidemiology
Mastitis is quite common among breastfeeding women. The WHO estimates that although incidences vary between 2.6% and 33%, the prevalence globally is approximately 10% of breastfeeding women. Most mothers who develop mastitis  usually do so within the first few weeks after delivery. Most breast infections occur within the first or second month after delivery or at the time of weaning </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 Congenital trigger thumb and can you explain it in depth? [/INST] Congenital trigger thumb is a trigger thumb in infants and young children. Triggering, clicking or snapping is observed by flexion or extension of the interphalangeal joint (IPJ). In the furthest stage, no extension is possible and there is a fixed flexion deformity of the thumb in the IPJ. Cause, natural history, prognosis and recommended treatment are controversial.

Signs and symptoms
Besides the clicking, snapping or triggering, a characteristic Notta nodule is commonly found on the palmar side at the metacarpophalangeal (MCP) joint. This nodule can be found by palpation. Children can also present a thumb which they cannot extend actively due to entrapment of the nodule to the A1 pulley. Some may even present with a fixed flexion deformity of the IPJ where no extension is possible.

Cause
It is unclear whether the cause of the trigger thumb is congenital or acquired. The occurrence of bilateral incidence and trigger thumbs in both children of twins are an indication for a congenital cause. Trigger thumb in children is also associated with trisomy of chromosome 13. For these reasons it was assumed that trigger thumbs in children are to be of congenital cause. However, more and more evidence which point towards an acquired cause have been found in recent studies. Therefore, the name pediatric trigger thumb is also widely used (and currently preferred by some) for the same disorder.

Diagnosis
Diagnosis of a trigger thumb is solely made by these clinical observations and further classified into four stages:

Treatment
There are several types of treatment for congenital trigger thumb, conservative and surgical.

Conservative
The conservative treatment consists of observation in time. Studies show that the trigger thumb spontaneously resolves in 49 months. According to Leung et al., trigger thumbs in infants resolve spontaneously in 63% of the cases. No residual deformities were found and there is no recurrence once resolved. Residual deformity is defined as persistent flexion deformities of the thumb and radial deviation at the IPJ. Extension exercises and splinting can be added to the observation. These two elements have favourable results in improvement in flexion impairment of the thumb. However, compared to observation, the benefit of merely extension exercises and splinting are still unclear.It has been recommended to attempt conservative treatment first, before attempting surgical treatment.

Surgical
Surgical treatment should be considered when the patient has a trigger thumb bilaterally and when the patient has a severe trigger thumb. Severe is defined as when the thumb is locked so that the thumb cannot be flexed or extended either passively or actively. Surgical treatment should also be considered when observation and/or splint therapy has not achieved sufficient results after 49 months. Unlike the surgical treatment given for adults, which is unambiguously a surgical release of the A1 pulley of the thumb, the optimum surgical treatment for infants has not yet been discerned. In case of infants, research has shown that only in 15% of the cases A1 pulley release alone is sufficient. In most of the cases there was an additional annular pulley structure distal to the A1 to be released resolving the triggering: the so-called Av pulley or variable pulley. Therefore, infants and adults need to be treated differently as the main problem is different.

Open vs. percutaneous
There are two types of surgery: open surgery which is mentioned above and percutaneous surgery. Unlike open surgery percutaneous surgery is done without exposing the anatomical structures beneath the skin. Research has shown that percutaneous surgery is a good alternative to open surgery. Percutaneous surgery is done with a needle that is inserted in the flexor sheath at the level of the A1 pulley. Before the needle insertion the thumb is placed in extension, whereas when the needle is already inserted the thumb will be put into semi-flexion, so that the needle can be moved and the palmar skin is movable </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 Brain tumor and can you explain it in depth? [/INST] A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondary tumors, which most commonly have spread from tumors located outside the brain, known as brain metastasis tumors. All types of brain tumors may produce symptoms that vary depending on the size of the tumor and the part of the brain that is involved. Where symptoms exist, they may include headaches, seizures, problems with vision, vomiting and mental changes. Other symptoms may include difficulty walking, speaking, with sensations, or unconsciousness.The cause of most brain tumors is unknown. Uncommon risk factors include exposure to vinyl chloride, Epstein–Barr virus, ionizing radiation, and inherited syndromes such as neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau Disease. Studies on mobile phone exposure have not shown a clear risk. The most common types of primary tumors in adults are meningiomas (usually benign) and astrocytomas such as glioblastomas. In children, the most common type is a malignant medulloblastoma. Diagnosis is usually by medical examination along with computed tomography (CT) or magnetic resonance imaging (MRI). The result is then often confirmed by a biopsy. Based on the findings, the tumors are divided into different grades of severity.Treatment may include some combination of surgery, radiation therapy and chemotherapy. Since the brain is the bodys only non-fungible organ, surgery carries a risk of the tumor returning. If seizures occur, anticonvulsant medication may be needed. Dexamethasone and furosemide are medications that may be used to decrease swelling around the tumor. Some tumors grow gradually, requiring only monitoring and possibly needing no further intervention. Treatments that use a persons immune system are being studied. Outcomes for malignant tumors vary considerably depending on the type of tumor and how far it has spread at diagnosis. Although benign tumors only grow in one area, they may still be life-threatening depending on their size and location. Malignant glioblastomas usually have very poor outcomes, while benign meningiomas usually have good outcomes. The average five-year survival rate for all (malignant) brain cancers in the United States is 33%.Secondary, or metastatic, brain tumors are about four times as common as primary brain tumors, with about half of metastases coming from lung cancer. Primary brain tumors occur in around 250,000 people a year globally, and make up less than 2% of cancers. In children younger than 15, brain tumors are second only to acute lymphoblastic leukemia as the most common form of cancer. In NSW Australia in 2005, the average lifetime economic cost of a case of brain cancer was AU$1.9 million, the greatest of any type of cancer.

Signs and symptoms
The signs and symptoms of brain tumors are broad. People may experience symptoms regardless of whether the tumor is benign (not cancerous) or cancerous. Primary and secondary brain tumors present with similar symptoms, depending on the location, size, and rate of growth of the tumor. For example, larger tumors in the frontal lobe can cause changes in the ability to think. However, a smaller tumor in an area such as Wernickes area (small area responsible for language comprehension) can result in a greater loss of function.

Headaches
Headaches as a result of raised intracranial pressure can be an early symptom of brain cancer. However, isolated headache without other symptoms is rare, and other symptoms including visual abnormalities may occur before headaches become common. Certain warning signs for headache exist which make the headache more likely to be associated with brain cancer. These are, as defined by the American Academy of Neurology: "abnormal neurological examination, headache worsened by Valsalva maneuver, headache causing awakening from sleep, new headache in the older population, progressively worsening headache, atypical headache features, or patients who do not fulfill the strict definition of migraine". Other associated signs are headaches that are worse in the morning or that subside after vomiting.

Location-specific symptoms
The brain is divided into lobes and each lobe or area has its own function. A tumor in any of these lobes may affect the areas performance. The symptoms experienced are often linked to the location of the tumor, but each person may experience something different.
Frontal lobe: Tumors may contribute to poor reasoning, inappropriate social behavior, personality changes, poor planning, lower inhibition, and decreased production of speech (Brocas area).
Temporal lobe: Tumors in this lobe may contribute to poor memory, loss of hearing, and difficulty in language comprehension (Wernickes area is located in this lobe).
Parietal lobe: Tumors here may result in poor interpretation of languages, difficulty with speaking, writing, drawing, naming, and recognizing, and poor spatial and visual perception.
Occipital lobe: Damage to this lobe may result in poor vision or loss of vision.
Cerebellum: Tumors in this area may cause poor balance, muscle movement, and posture.
Brain stem: Tumors on the brainstem can cause seizures, endocrine problems, respiratory changes, visual changes, headaches and partial paralysis.

Behavior changes
A persons personality may be altered due to the tumor damaging lobes of the brain. Since the frontal, temporal, and parietal lobes control inhibition, emotions, mood, judgement, reasoning, and behavior, a tumor in those regions can cause inappropriate social behavior, temper tantrums, laughing at things which merit no laughter, and even psychological symptoms such as depression and anxiety. More research is needed into the effectiveness and safety of medication for depression in people with brain tumors.Personality changes can have damaging effects such as unemployment, unstable relationships, and a lack of control.

Cause
Epidemiological studies are required to determine risk factors. Aside from exposure to vinyl chloride or ionizing radiation, there are no known environmental factors associated with brain tumors. Mutations and deletions of tumor suppressor genes, such as P53, are thought to be the cause of some forms of brain tumor. Inherited conditions, such as Von Hippel–Lindau disease, tuberous sclerosis, multiple endocrine neoplasia, and neurofibromatosis type 2 carry a high risk for the development of brain tumors. People with celiac disease have a slightly increased risk of developing brain tumors. Smoking has been suggested to increase the risk but evidence remains unclear.Although studies have not shown any link between cell phone or mobile phone radiation and the occurrence of brain tumors, the World Health Organization has classified mobile phone radiation on the IARC scale into Group 2B – possibly carcinogenic. The claim that cell phone usage may cause brain cancer is likely based on epidemiological studies which observed a slight increase in glioma risk among heavy users of wireless and cordless phones. When those studies were conducted, GSM (2G) phones were in use. Modern, third-generation (3G) phones emit, on average, about 1% of the energy emitted by those GSM (2G) phones, and therefore the finding of an association between cell phone usage and increased risk of brain cancer is not based upon current phone usage.

Pathophysiology
Meninges
Human brains are surrounded by a system of connective tissue membranes called meninges that separate the brain from the skull. This three-layered covering is composed of (from the outside in) the dura mater, arachnoid mater, and pia mater. The arachnoid and pia are physically connected and thus often considered as a single layer, the leptomeninges. Between the arachnoid mater and the pia mater is the subarachnoid space which contains cerebrospinal fluid (CSF). This fluid circulates in the narrow spaces between cells and through the cavities in the brain called ventricles, to support and protect the brain tissue. Blood vessels enter the central nervous system through the perivascular space above the pia mater. The cells in the blood vessel walls are joined tightly, forming the blood–brain barrier which protects the brain from toxins that might enter through the blood.Tumors of the meninges are meningiomas and are often benign. Though not technically a tumor of brain tissue, they are often considered brain tumors since they protrude into the space where the brain is, causing symptoms. Since they are usually slow-growing tumors, meningiomas can be quite large by the time symptoms appear.

Brain matter
The brains of humans and other vertebrates are composed of very soft tissue and have a gelatin-like texture. Living brain tissue has a pink tint in color on the outside (gray matter), and nearly complete white on the inside (white matter), with subtle variations in color. The three largest divisions of the brain are:

Cerebral cortex
Brainstem
CerebellumThese areas are composed of two broad classes of cells: neurons and glia. These two types are equally numerous in the brain as a whole, although glial cells outnumber neurons roughly 4 to 1 in the cerebral cortex. Glia come in several types, which perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development. Primary tumors of the glial cells are called gliomas and often are malignant by the time they are diagnosed.The thalamus and hypothalamus are major divisions of the diencephalon, with the pituitary gland and pineal gland attached at the bottom; tumors of the pituitary and pineal gland are often benign.The brainstem lies between the large cerebral cortex and the spinal cord. It is divided into the midbrain, pons, and medulla oblongata.

Spinal cord
The spinal cord is considered a part of the central nervous system. It is made up of the same cells as the brain: neurons and glial cells.

Diagnosis
Although there is no specific or singular symptom or sign, the presence of a combination of symptoms and the lack of corresponding indications of other causes can be an indicator for investigation towards the possibility of a brain tumor. Brain tumors have similar characteristics and obstacles when it comes to diagnosis and therapy with tumors located elsewhere in the body. However, they create specific issues that follow closely to the properties of the organ they are in.The diagnosis will often start by taking a medical history noting medical antecedents, and current symptoms. Clinical and laboratory investigations will serve to exclude infections as the cause of the symptoms. Examinations in this stage may include the eyes, otolaryngological (or ENT) and electrophysiological exams. The use of electroencephalography (EEG) often plays a role in the diagnosis of brain tumors.Brain tumors, when compared to tumors in other areas of the body, pose a challenge for diagnosis. Commonly, radioactive tracers are uptaken in large volumes in tumors due to the high activity of tumor cells, allowing for radioactive imaging of the tumor. However, most of the brain is separated from the blood by the blood-brain barrier (BBB), a membrane that exerts a strict control over what substances are allowed to pass into the brain. Therefore, many tracers that may reach tumors in other areas of the body easily would be unable to reach brain tumors until there was a disruption of the BBB by the tumor. Disruption of the BBB is well imaged via MRI or CT scan, and is therefore regarded as the main diagnostic indicator for malignant gliomas, meningiomas, and brain metastases.Swelling or obstruction of the passage of cerebrospinal fluid (CSF) from the brain may cause (early) signs of increased intracranial pressure which translates clinically into headaches, vomiting, or an altered state of consciousness, and in children changes to the diameter of the skull and bulging of the fontanelles. More complex symptoms such as endocrine dysfunctions should alarm doctors not to exclude brain tumors.A bilateral temporal visual field defect (due to compression of the optic chiasm) or dilation of the pupil, and the occurrence of either slowly evolving or the sudden onset of focal neurologic symptoms, such as cognitive and behavioral impairment (including impaired judgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, or more severe symptoms such as tremors, paralysis on one side of the body hemiplegia, or (epileptic) seizures in a patient with a negative history for epilepsy, should raise the possibility of a brain tumor.

Imaging
Medical imaging plays a central role in the diagnosis of brain tumors. Early imaging methods – invasive and sometimes dangerous – such as pneumoencephalography and cerebral angiography have been abandoned in favor of non-invasive, high-resolution techniques, especially magnetic resonance imaging (MRI) and computed tomography (CT) scans, though MRI is typically the reference standard used. Neoplasms will often show as differently colored masses (also referred to as processes) in CT or MRI results.
Benign brain tumors often show up as hypodense (darker than brain tissue) mass lesions on CT scans. On MRI, they appear either hypodense or isointense (same intensity as brain tissue) on T1-weighted scans, or hyperintense (brighter than brain tissue) on T2-weighted MRI, although the appearance is variable.
Contrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either CT or MRI scans in most malignant primary and metastatic brain tumors.
Pressure areas where the brain tissue has been compressed by a tumor also appear hyperintense on T2-weighted scans and might indicate the presence a diffuse neoplasm due to an unclear outline. Swelling around the tumor known as peritumoral edema can also show a similar result.This is because these tumors disrupt the normal functioning of the BBB and lead to an increase in its permeability. More recently, advancements have been made to increase the utility of MRI in providing physiological data that can help to inform diagnosis and prognosis. Perfusion Weighted Imaging (PWI) and Diffusion Weighted Imaging (DWI) are two MRI techniques that reviews have been shown to be useful in classifying tumors by grade, which was not previously viable using only structural imaging. However, these techniques cannot alone diagnose high- versus low-grade gliomas, and thus the definitive diagnosis of brain tumor should only be confirmed by histological examination of tumor tissue samples obtained either by means of brain biopsy or open surgery. The histological examination is essential for determining the appropriate treatment and the correct prognosis. This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and follow-up examination of prepared tissues after immunohistochemical staining or genetic analysis.

Pathology
Tumors have characteristics that allow the determination of malignancy and how they will evolve, and determining these characteristics will allow the medical team to determine the management plan.Anaplasia or dedifferentiation: loss of differentiation of cells and of their orientation to one another and blood vessels, a characteristic of anaplastic tumor tissue. Anaplastic cells have lost total control of their normal functions and many have deteriorated cell structures. Anaplastic cells often have abnormally high nuclear-to-cytoplasmic ratios, and many are multinucleated. Additionally, the nucleus of anaplastic cells is usually unnaturally shaped or oversized. Cells can become anaplastic in two ways: neoplastic tumor cells can dedifferentiate to become anaplasias (the dedifferentiation causes the cells to lose all of their normal structure/function), or cancer stem cells can increase their capacity to multiply (i.e., uncontrollable growth due to failure of differentiation).Atypia: an indication of abnormality of a cell (which may be indicative of malignancy). Significance of the abnormality is highly dependent on context.Neoplasia: the (uncontrolled) division of cells. As such, neoplasia is not problematic but its consequences are: the uncontrolled division of cells means that the mass of a neoplasm increases in size, and in a confined space such as the intracranial cavity this quickly becomes problematic because the mass invades the space of the brain pushing it aside, leading to compression of the brain tissue and increased intracranial pressure and destruction of brain parenchyma. Increased intracranial pressure (ICP) may be attributable to the direct mass effect of the tumor, increased blood volume, or increased cerebrospinal fluid (CSF) volume, which may, in turn, have secondary symptoms.Necrosis: the (premature) death of cells, caused by external factors such as infection, toxin or trauma. Necrotic cells send the wrong chemical signals which prevent phagocytes from disposing of the dead cells, leading to a buildup of dead tissue, cell debris and toxins at or near the site of the necrotic cellsArterial and venous hypoxia, or the deprivation of adequate oxygen supply to certain areas of the brain, occurs when a tumor makes use of nearby blood vessels for its supply of blood and the neoplasm enters into competition for nutrients with the surrounding brain tissue. More generally a neoplasm may cause release of metabolic end products (e.g., free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (e.g., cytokines) that disrupt normal parenchymal function.

Classification
Tumors can be benign or malignant, can occur in different parts of the brain, and may be classified as primary or secondary. A primary tumor is one that has started in the brain, as opposed to a metastatic tumor, which is one that has spread to the brain from another area of the body. The incidence of metastatic tumors is approximately four times greater than primary tumors. Tumors may or may not be symptomatic: some tumors are discovered because the patient has symptoms, others show up incidentally on an imaging scan, or at an autopsy.Grading of the tumors of the central nervous system commonly occurs on a 4-point scale (I-IV) created by the World Health Organization in 1993. Grade I tumors are the least severe and commonly associated with long-term survival, with severity and prognosis worsening as the grade increases. Low-grade tumors are often benign, while higher grades are aggressively malignant and/or metastatic. Other grading scales do exist, many based upon the same criteria as the WHO scale and graded from I-IV.

Primary
The most common primary brain tumors are:
Gliomas (50.4%)
Meningiomas (20.8%)
Pituitary adenomas (15%)
Nerve sheath tumors (10%)These common tumors can also be organized according to tissue of origin as shown below:

Secondary
Secondary tumors of the brain are metastatic and have invaded the brain from cancers originating in other organs. This means that a cancerous neoplasm has developed in another organ elsewhere in the body and that cancer cells have leaked from that primary tumor and then entered the lymphatic system and blood vessels.  They then circulate through the bloodstream, and are deposited in the brain. There, these cells continue growing and dividing, becoming another invasive neoplasm of primary cancers tissue. Secondary tumors of the brain are very common in the terminal phases of patients with an incurable metastasized cancer; the most common types of cancers that bring about secondary tumors of the brain are lung cancer, breast cancer, malignant melanoma, kidney cancer, and colon cancer (in decreasing order of frequency).Secondary brain tumors are more common than primary ones; in the United States, there are about 170,000 new cases every year. Secondary brain tumors are the most common cause of tumors in the intracranial cavity. The skull bone structure can also be subject to a neoplasm that by its very nature reduces the volume of the intracranial cavity, and can damage the brain.

By behavior
Brain tumors or intracranial neoplasms can be cancerous (malignant) or non-cancerous (benign). However, the definitions of malignant or benign neoplasms differ from those commonly used in other types of cancerous or non-cancerous neoplasms in the body.
In cancers elsewhere in the body, three malignant properties differentiate benign tumors from malignant forms of cancer: benign tumors are self-limited and do not invade or metastasize. Characteristics of malignant tumors include:
uncontrolled mitosis (growth by division beyond the normal limits)
anaplasia: the cells in the neoplasm have an obviously different form (in size and shape). Anaplastic cells display marked pleomorphism. The cell nuclei are characteristically extremely hyperchromatic (darkly stained) and enlarged; the nucleus might have the same size as the cytoplasm of the cell (nuclear-cytoplasmic ratio may approach 1:1, instead of the normal 1:4 or 1:6 ratio). Giant cells – considerably larger than their neighbors – may form and possess either one enormous nucleus or several nuclei (syncytia). Anaplastic nuclei are variable and bizarre in size and shape.
invasion or infiltration (medical literature uses these terms as synonymous equivalents. However, for clarity, the articles that follow adhere to a convention that they mean slightly different things; this convention is not followed outside these articles):
Invasion or invasiveness is the spatial expansion of the tumor through uncontrolled mitosis, in the sense that the neoplasm invades the space occupied by adjacent tissue, thereby pushing the other tissue aside and eventually compressing the tissue. Often these tumors are associated with clearly outlined tumors in imaging.
Infiltration is the behavior of the tumor either to grow (microscopic) tentacles that push into the surrounding tissue (often making the outline of the tumor undefined or diffuse) or to have tumor cells "seeded" into the tissue beyond the circumference of the tumorous mass; this does not mean that an infiltrative tumor does not take up space or does not compress the surrounding tissue as it grows, but an infiltrating neoplasm makes it difficult to say where the tumor ends and the healthy tissue starts.
metastasis (spread to other locations in the body via lymph or blood).Of the above malignant characteristics, some elements do not apply to primary neoplasms of the brain:

Primary brain tumors rarely metastasize to other organs; some forms of primary brain tumors can metastasize but will not spread outside the intracranial cavity or the central spinal canal. Due to the BBB, cancerous cells of a primary neoplasm cannot enter the bloodstream and get carried to another location in the body. (Occasional isolated case reports suggest spread of certain brain tumors outside the central nervous system, e.g. bone metastasis of glioblastoma multiforme.)
Primary brain tumors generally are invasive (i.e. they will expand spatially and intrude into the space occupied by other brain tissue and compress those brain tissues); however, some of the more malignant primary brain tumors will infiltrate the surrounding tissue.

By genetics
In 2016, the WHO restructured their classifications of some categories of gliomas to include distinct genetic mutations that have been useful in differentiating tumor types, prognoses, and treatment responses. Genetic mutations are typically detected via immunohistochemistry, a technique that visualizes the presence or absence of a targeted protein via staining.
Mutations in IDH1 and IDH2 genes are commonly found in low-grade gliomas
Loss of both IDH genes combined with loss of chromosome arms 1p and 19q indicates the tumor is an oligodendroglioma
Loss of TP53 and ATRX characterizes astrocytomas
Genes EGFR, TERT, and PTEN, are commonly altered in gliomas and are useful in differentiating tumor grade and biology

Specific types
Anaplastic astrocytoma, Anaplastic oligodendroglioma, Astrocytoma, Central neurocytoma, Choroid plexus carcinoma, Choroid plexus papilloma, Choroid plexus tumor, Colloid cyst, Dysembryoplastic neuroepithelial tumour, Ependymal tumor, Fibrillary astrocytoma, Giant-cell glioblastoma, Glioblastoma multiforme, Gliomatosis cerebri, Gliosarcoma, Hemangiopericytoma, Medulloblastoma, Medulloepithelioma, Meningeal carcinomatosis, Neuroblastoma, Neurocytoma, Oligoastrocytoma, Oligodendroglioma, Optic nerve sheath meningioma, Pediatric ependymoma, Pilocytic astrocytoma, Pinealoblastoma, Pineocytoma, Pleomorphic anaplastic neuroblastoma, Pleomorphic xanthoastrocytoma, Primary central nervous system lymphoma, Sphenoid wing meningioma, Subependymal giant cell astrocytoma, Subependymoma, Trilateral retinoblastoma.

Treatment
A medical team generally assesses the treatment options and presents them to the person affected and their family. Various types of treatment are available depending on tumor type and location, and may be combined to produce the best chances of survival:
Surgery: complete or partial resection of the tumor with the objective of removing as many tumor cells as possible.
Radiotherapy: the most commonly used treatment for brain tumors; the tumor is irradiated with beta, x rays or gamma rays.
Chemotherapy: a treatment option for cancer, however, it is not always used to treat brain tumors as the blood-brain barrier can prevent some drugs from reaching the cancerous cells.
A variety of experimental therapies are available through clinical trials.Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical removal and other factors specific to each case.Standard care for anaplastic oligodendrogliomas and anaplastic oligoastrocytomas is surgery followed by radiotherapy. One study found a survival benefit for the addition of chemotherapy to radiotherapy after surgery, compared with radiotherapy alone.

Surgery
The primary and most desired course of action described in medical literature is surgical removal (resection) via craniotomy. Minimally invasive techniques are becoming the dominant trend in neurosurgical oncology. The main objective of surgery is to remove as many tumor cells as possible, with complete removal being the best outcome and cytoreduction ("debulking") of the tumor otherwise. A Gross Total Resection (GTR) occurs when all visible signs of the tumor are removed, and subsequent scans show no apparent tumor. In some cases access to the tumor is impossible and impedes or prohibits surgery.
Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically.
Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenomas require a craniotomy (opening of the skull) for their removal. Radiotherapy, including stereotactic approaches, is reserved for inoperable cases.Several current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with 5-aminolevulinic acid that causes them to fluoresce. Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors.Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy rather than surgery and the prognosis in such cases is determined by the primary tumor, and is generally poor.

Radiation therapy
The goal of radiation therapy is to kill tumor cells while leaving normal brain tissue unharmed. In standard external beam radiation therapy, multiple treatments of standard-dose "fractions" of radiation are applied to the brain. This process is repeated for a total of 10 to 30 treatments, depending on the type of tumor. This additional treatment provides some patients with improved outcomes and longer survival rates.Radiosurgery is a treatment method that uses computerized calculations to focus radiation at the site of the tumor while minimizing the radiation dose to the surrounding brain. Radiosurgery may be an adjunct to other treatments, or it may represent the primary treatment technique for some tumors. Forms used include stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery.Radiotherapy is the most common treatment for secondary brain tumors. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam "whole-brain radiotherapy treatment" (WBRT) or "whole-brain irradiation" may be suggested if there is a risk that other secondary tumors will develop in the future. Stereotactic radiotherapy is usually recommended in cases involving fewer than three small secondary brain tumors. Radiotherapy may be used following, or in some cases in place of, resection of the tumor. Forms of radiotherapy used for brain cancer include external beam radiation therapy, the most common, and brachytherapy and proton therapy, the last especially used for children.
People who receive stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone. Results of a 2021 systematic review found that when using SRS as the initial treatment, survival or death related to brain metastasis was not greater than alone versus SRS with WBRT.Postoperative conventional daily radiotherapy improves survival for adults with good functional well-being and high grade glioma compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.

Chemotherapy
Patients undergoing chemotherapy are administered drugs designed to kill tumor cells. Although chemotherapy may improve overall survival in patients with the most malignant primary brain tumors, it does so in only about 20 percent of patients. Chemotherapy is often used in young children instead of radiation, as radiation may have negative effects on the developing brain. The decision to prescribe this treatment is based on a patients overall health, type of tumor, and extent of cancer. The toxicity and many side effects of the drugs, and the uncertain outcome of chemotherapy in brain tumors puts this treatment further down the line of treatment options with surgery and radiation therapy preferred.UCLA Neuro-Oncology publishes real-time survival data for patients with a diagnosis of glioblastoma multiforme. They are the only institution in the United States that displays how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high-grade glioma tumors.Genetic mutations have significant effects on the effectiveness of chemotherapy. Gliomas with IDH1 or IDH2 mutations respond better to chemotherapy than those without the mutation. Loss of chromosome arms 1p and 19q also indicate better response to chemoradiation.

Other
A shunt may be used to relieve symptoms caused by intracranial pressure, by reducing the build-up of fluid (hydrocephalus) caused by the blockage of the free flow of cerebrospinal fluid.

Prognosis
The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma multiforme has a median survival of only 12 months even with aggressive chemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type, focal brainstem gliomas in children, seems open to exceptional prognosis and long-term survival has frequently been reported.Prognosis is also affected by presentation of genetic mutations. Certain mutations provide better prognosis than others. IDH1 and IDH2 mutations in gliomas, as well as deletion of chromosome arms 1p and 19q, generally indicate better prognosis. TP53, ATRX, EGFR, PTEN, and TERT mutations are also useful in determining prognosis.

Glioblastoma multiforme
Glioblastoma multiforme (GBM) is the most aggressive (grade IV) and most common form of a malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer, then by chemotherapy, such as temozolomide. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to relieve symptoms. Experimental treatments include targeted therapy, gamma knife radiosurgery, boron neutron capture therapy, gene therapy also chemowafer implants.

Oligodendrogliomas
Oligodendrogliomas are incurable but slowly progressive malignant brain tumors. They can be treated with surgical resection, chemotherapy, radiotherapy or a combination. For some suspected low-grade (grade II) tumors, only a course of watchful waiting and symptomatic therapy is opted for. These tumors show a high frequency of co-deletions of the p and q arms of chromosome 1 and chromosome 19 respectively (1p19q co-deletion) and have been found to be especially chemosensitive with one report claiming them to be one of the most chemosensitive tumors. A median survival of up to 16.7 years has been reported for grade II oligodendrogliomas.

Acoustic neuroma
Acoustic neuromas are non-cancerous tumors. They can be treated with surgery, radiation therapy, or observation. Early intervention with surgery or radiation is recommended to prevent progressive hearing loss.

Epidemiology
Figures for incidences of cancers of the brain show a significant difference between more- and less-developed countries (the less-developed countries have lower incidences of tumors of the brain). This could be explained by undiagnosed tumor-related deaths (patients in extremely poor situations do not get diagnosed, simply because they do not have access to the modern diagnostic facilities required to diagnose a brain tumor) and by deaths caused by other poverty-related causes that preempt a patients life before tumors develop or tumors become life-threatening. Nevertheless, statistics suggest that certain forms of primary brain tumors are more common among certain populations.The incidence of low-grade astrocytoma has not been shown to vary significantly with nationality. However, studies examining the incidence of malignant central nervous system (CNS) tumors have shown some variation with national origin. Since some high-grade lesions arise from low-grade tumors, these trends are worth mentioning. Specifically, the incidence of CNS tumors in the United States, Israel, and the Nordic countries is relatively high, while Japan and Asian countries have a lower incidence. These differences probably reflect some biological differences as well as differences in pathologic diagnosis and reporting.
Worldwide data on incidence of cancer can be found at the WHO (World Health Organisation) and is handled by the IARC (International Agency for Research on Cancer) located in France.

United States
In the United States in 2015, approximately 166,039 people were living with brain or other central nervous system tumors. Over 2018, it was projected that there would be 23,880 new cases of brain tumors and 16,830 deaths in 2018 as a result, accounting for 1.4 percent of all cancers and 2.8 percent of all cancer deaths. Median age of diagnosis was 58 years old, while median age of death was 65. Diagnosis was slightly more common in males, at approximately 7.5 cases per 100 000 people, while females saw 2 fewer at 5.4. Deaths as a result of brain cancer were 5.3 per 100 000 for males, and 3.6 per 100 000 for females, making brain cancer the 10th leading cause of cancer death in the United States. Overall lifetime risk of developing brain cancer is approximated at 0.6 percent for men and women.

UK
Brain, other CNS or intracranial tumors are the ninth most common cancer in the UK (around 10,600 people were diagnosed in 2013), and it is the eighth most common cause of cancer death (around 5,200 people died in 2012).  White British patients with brain tumour are 30% more likely to die within a year of diagnosis than patients from other ethnicities.  The reason for this is unknown.

Children
In the United States more than 28,000 people under 20 are estimated to have a brain tumor. About 3,720 new cases of brain tumors are expected to be diagnosed in those under 15 in 2019. Higher rates were reported in 1985–1994 than in 1975–1983. There is some debate as to the reasons; one theory is that the trend is the result of improved diagnosis and reporting, since the jump occurred at the same time that MRIs became available widely, and there was no coincident jump in mortality. Central nervous system tumors make up 20–25 percent of cancers in children.The average survival rate for all primary brain cancers in children is 74% </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 Hiccup and can you explain it in depth? [/INST] A hiccup (scientific name singultus, from a Latin word meaning "to catch ones breath while sobbing"; also spelled hiccough) is an involuntary contraction (myoclonic jerk) of the diaphragm that may repeat several times per minute. The hiccup is an involuntary action involving a reflex arc. Once triggered, the reflex causes a strong contraction of the diaphragm followed about a quarter of a second later by closure of the vocal cords, which results in the "hic" sound.
Hiccups may occur individually, or they may occur in bouts. The rhythm of the hiccup, or the time between hiccups, tends to be relatively constant. A bout of hiccups generally resolves itself without intervention, although many home remedies are often used to attempt to shorten the duration. Medical treatment is occasionally necessary in cases of chronic hiccups.

Incidence
Hiccups affect people of all ages, even being observed in utero. They become less frequent with advancing age. Intractable hiccups, lasting more than a month, are more common in adults. While males and females are affected equally often, men are more likely to develop hiccups lasting more than 48 hours. Dogs may also get hiccups.

Signs and symptoms
A hiccup consists of a single or a series of breathing diaphragm spasms, of variable spacing and duration, and a brief (less than one half second), unexpected, shoulder, abdomen, throat, or full body tremor. Hiccups may present as an audible chirp, squeak, "hupp", or if controlled, a quick inhaling gasp, sigh, or sniff. They may also present as brief but distracting or painful interruptions in normal breathing, with sudden momentary pain of the throat, chest, or abdomen.

Causes
Pathophysiological causes
Swallowing air excessively
Gastroesophageal reflux
Hiatal hernia
Rapid eating
Carbonated beverages, alcohol, dry breads, and some spicy foods
Opiate drug use
Laughing vigorously or for a long timeHiccups may be triggered by a number of common human conditions. In rare cases, they can be a sign of serious medical problems. In rare cases, hiccups can be the sole symptom of myocardial infarction.

Pre-phrenic nucleus irritation of medulla
Kidney failure

CNS disorders
Stroke
Multiple sclerosis
Meningitis

Nerve damage
Damage to the vagus nerve after surgery

Other known associations
Although no clear pathophysiological mechanism has been described, hiccups is known to have been the initial symptom of Plasmodium vivax malaria in at least one documented case.

Evolutionary theories
The burping reflex hypothesis
A leading hypothesis is that hiccups evolved to facilitate greater milk consumption in young mammals. The coordination of breathing and swallowing during suckling is a complicated process. Some air inevitably enters the stomach, occupying space that could otherwise be optimally used for calorie rich milk.The hypothesis suggests that the presence of an air bubble in the stomach stimulates the sensory (afferent) limb of the reflex through receptors in the stomach, esophagus and along the underside of the diaphragm. This triggers the active part of the hiccup (efferent limb), sharply contracting the muscles of breathing and relaxing the muscles of the esophagus, then closing the vocal cords to prevent air from entering the lungs. This creates suction in the chest, pulling air from the stomach up into the esophagus. As the respiratory muscles relax the air is expelled through the mouth, effectively "burping" the animal.There are a number of characteristics of hiccups that support this theory. The burping of a suckling infant may increase its capacity for milk by more than 15-25%, bringing a significant survival advantage. There is a strong tendency for infants to get hiccups, and although the reflex persists throughout life it decreases in frequency with age. The location of the sensory nerves that trigger the reflex suggests it is a response to a condition in the stomach. The component of the reflex that suppresses peristalsis in the esophagus while the airway is being actively blocked suggests the esophagus is involved. Additionally, hiccups are only described in mammals - the group of animals that share the trait of suckling their young.

Phylogenetic hypothesis
An international respiratory research group composed of members from Canada, France, and Japan proposed that the hiccup is an evolutionary remnant of earlier amphibian respiration. Amphibians such as tadpoles gulp air and water across their gills via a rather simple motor reflex akin to mammalian hiccuping. The motor pathways that enable hiccuping form early during fetal development, before the motor pathways that enable normal lung ventilation form. Thus, the hiccup is evolutionarily antecedent to modern lung respiration.
Additionally, this group (C. Straus et al.) points out that hiccups and amphibian gulping are inhibited by elevated CO2 and may be stopped by GABAB receptor agonists, illustrating a possible shared physiology and evolutionary heritage. These proposals may explain why premature infants spend 2.5% of their time hiccuping, possibly gulping like amphibians, as their lungs are not yet fully formed.The phylogenetic hypothesis may explain hiccups as an evolutionary remnant, held over from our amphibious ancestors. This hypothesis has been questioned because of the complexity of the mammalian hiccup reflex compared to the amphibian breathing reflex, the fact that it does not explain the reason for glottic closure, and because the very short contraction of the hiccup is unlikely to have a significant strengthening effect on the slow-twitch muscles of respiration.Fetal intrauterine hiccups are of two types. The physiological type occurs prior to twenty-eight weeks after conception and tends to last five to ten minutes. These hiccups are part of fetal development and are associated with the myelination of the phrenic nerve, which primarily controls the thoracic diaphragm.The phylogenetic and the burping hypotheses are not mutually exclusive. The phylogeny hypothesis could explain how the hiccup reflex might have evolved, while the "Burping Hypothesis" could explain why it would offer enough of an evolutionary advantage to persist and increase in complexity.

Duration
Episodes of hiccups usually last just a few minutes, doing nothing worse than annoying those affected and amusing bystanders, but prolonged attacks can be serious, with a cause difficult to diagnose. Such attacks can cause significant morbidity and even death. An episode lasting more than a few minutes is termed a bout; a bout of over 48 hours is termed persistent or protracted. Hiccups lasting longer than a month are termed intractable. In many cases, only a single hemidiaphragm, usually the left one, is affected, although both may be involved.

Treatment
Hiccups are normally waited out, as any fit of them will usually pass quickly. Folk cures for hiccups are common and varied, but no effective standard for stopping hiccups has been documented. Hiccups are treated medically only in severe and persistent (termed "intractable") cases.Numerous medical remedies exist but no particular treatment is known to be especially effective, generally because of a lack of high-quality evidence. Many drugs have been used, such as baclofen, chlorpromazine, metoclopramide, gabapentin, and various proton-pump inhibitors. Hiccups that are secondary to some other cause, like gastroesophageal reflux disease or esophageal webs, are dealt with by treating the underlying disorder. The phrenic nerve can be blocked temporarily with injection of 0.5% procaine, or permanently with bilateral phrenicotomy or other forms of surgical destruction. Even this rather drastic treatment does not cure some cases, however.Haloperidol, metoclopramide, and chlorpromazine are used in cases of intractable hiccups. Effective treatment with sedatives often requires a dose that renders the person either unconscious or highly lethargic. Hence, medicating with sedatives is only appropriate short-term, as the affected individual cannot continue with normal life activities while under their effect.A vagus nerve stimulator has been used with an intractable case of hiccups. "It sends rhythmic bursts of electricity to the brain by way of the vagus nerve, which passes through the neck. The Food and Drug Administration approved the vagus nerve stimulator in 1997 as a way to control seizures in some patients with epilepsy."Persistent digital rectal massage has also been proven effective in terminating intractable hiccups.

Folk remedies
There are many superstitious and folk remedies for hiccups, including headstanding, drinking a glass of water upside-down, being frightened by someone, breathing into a bag, eating a large spoonful of peanut butter and placing sugar on or under the tongue.Acupressure, either through actual function or placebo effect, may cure hiccups in some people. For example, one technique is to relax the chest and shoulders and find the deepest points of the indentations directly below the protrusions of the collarbones. The index or middle fingers are inserted into the indents and pressed firmly for sixty seconds as long, deep breaths are taken.A simple treatment involves increasing the partial pressure of CO2 and inhibiting diaphragm activity by holding ones breath or rebreathing into a paper bag. Other potential remedies suggested by NHS Choices include pulling the knees up to the chest and leaning forward, sipping ice-cold water and swallowing some granulated sugar.Drinking through a straw with the ears plugged is a folk remedy that can be successful. In 2021 a scientific tool with a similar basis was tested on 249 hiccups subjects; the results were published in the Journal of the American Medical Association (JAMA). This device is named FISST (Forced Inspiratory Suction and Swallow Tool) and branded as "HiccAway". This study supports the use of FISST as an option to stop transient hiccups, with more than 90% of participants reporting better results than home remedies </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 Papillary hidradenoma and can you explain it in depth? [/INST] A papillary hidradenoma, also termed hidradenoma papilliferum or mammary-like gland adenoma of the vulva, is a rare, but nonetheless most common benign tumor that occurs in and between anal and genital regions (i.e. anogenital  area) of females. These hidradenomas are sharply circumscribed, nodular tumors that usually develop in womens anogenital area (particularly the vulva) but uncommonly occur in other sites in women and men. Papillary hidradenomas that develop outside of the anogenital region are termed ecctopic papillary hidradenomas or ectopic hidradenoma papilliferums.Anogenital papillary hidradenomas are regarded as tumors that form in anogenital mammary–like glands (MLAGs); MLAGs are a type of apocrine gland. MLAGs were once classified as abnormally located breast tissue glands (see accessory breast tissue@ https://doi.org/10.53347/rID-11125) but are now considered to be normal components of the anogenital region. Microscopically, papillary hidradenomas often resemble certain types of breast tumors. Ectopic papillary hidradenomas are thought to be tumors of apocrine glands which have an as yet unclear relationship to MLAGs.Typically, papillary hidradenomas are solitary, slow-growing, small tumors that may have been present for months to many years before the time of diagnosis. The tumors are usually symptomless but may be intermittently or constantly painful, become ulcerated, and exhibit minor levels of bleeding. The pain resulting from these tumors may be simple tenderness, more or less constant usually mild pain, or, in females, dyspareunia, i.e. pain during and just after sexual intercourse.Rarely, papillary hidradenomas have progressed to what appear to be 1) in situ malignancies (i.e. malignancies that have neither metastasized nor invaded beyond the layer of tissue where they arose); 2) locally invasive malignancies; or 3) complex tumors intermixed with other malignancies such as extramammary Paget disease, melanoma, and squamous cell carcinoma. Furthermore, benign papillary hidradenoma tumors may be confused clinically with cancerous tumors and recent studies have indicated that other types of tumors have often been mistakenly diagnosed as papillary hidradenomas. Papillary hidradenomas, particularly ectopic papillary hidradenomas, require further study to better define the criteria for their diagnosis.

Presentation
In a review of 264 women diagnosed with anogenital papillary hidradenomas, patients ranged in age from 25 to 82 years (median: 49 years); in 25 cases where the information was available, the tumors had been present for 2–120 months (median: 12 months) with 13 patients reporting their tumors presence for less than 1 year before diagnosis. All patients had a solitary tumor in the anogenital area except for one patient who presented with four clustered tumors. Most tumors involved the vulva (71.6%) and areas around the anus (14%) or space between the anus and vulva, i.e. the perineum (3.8%). Their lesions ranged in size from 0.2 to 2 centimeters (cm.) in largest dimension (median: 0.7 cm.). Smaller studies on one or a few females with anogenital papillary hidradenomas found that the tumors commonly presented as asymptomatic, well-confined, skin-colored, red, or bluish nodules in women of Caucasian origin between the ages of 25–66 years. The nodules were solid or cystic; 0.4 to 2.5 cm. in widest dimension; and usually located in the grooves (termed interlabial sulci or interlabial folds) between the labia majora and labia minora, the clitoris, or the region between the vulva and anus (i.e. Frenulum of labia minora). Ectopic papillary hidradenomas in women have been reported to occur on the scalp, eyelid, cheek, forehead, face, ear canal, and back. Nearly 50% of ectopic papillary hidradenoma have been diagnosed in men; these have occurred on the thigh, arm, armpit, face and eyelid. While usually symptomless, patients may complain that the tumor is ulcerated, bleeds, or is painful. This pain may be simple tenderness, more or less constant but usually mild, or, in females with anogenital lesions, dyspareunia. The rare cases of ectopic papillary hidradenoma in the external auditory canal have presented with unilateral conductive hearing loss sometimes associated with ear pain, drainage of ear fluid, or weakness of a facial muscle(s).

Histopathology
Microscopic histopathological analyses of papillary hidradenoma tumors typically reveal a nodule in the dermis, i.e. layer of skin between the epidermis and subcutaneous tissue. The tumor consists of complex patterns of interconnecting tubular and papillary (i.e. thin finger-like or frond-like) structures. These structures are lined with glandular epithelial and myoepithelial cells. The glandular epithelial cells appear to be excessively proliferating in the ducts leading to the epidermis and show oxyphilic changes, (i.e. cytoplasm filled with  large mitochondria, glycogen, and ribosomes) while the myoepithelial cells often appear clear cell-like, i.e. have uncolored cytoplasm when stained with hematoxylin and eosin. The histopathology of anogenital and ectopic papillary hidradenomas are similar to each other.

Immunohistochemistry
Immunohistochemical analyses of anogenital papillary hidradenoma tumors have detected the expression of both the estrogen and progesterone receptors in 18 and the androgen receptor in 4 of 20 cases. In another study of anogenital papillary hidradenomas, expression of the estrogen receptor was restricted to the tumors glandular epithelial cells while the tumors myoepithelial cells expressed tumor protein p63 and alpha-smooth muscle actin protein. Presence of the estrogen and progesterone receptors may underlie the female prevalence of anogenital papillary hidradenomas as well as their development in females only after puberty. The anogenital tumor cells may also express vimentin, various cytokeratin proteins, and in a minority of cases the DNA of human papillomavirus (infection by this virus and the presence of its DNA does not appear involved in the development of papillary hidradenoma). These immunohistochemistry findings have not as yet been reported in atypical papillary hidradenomas.

Gene and signaling pathway abnormalities
Several studies have reported the presence in anogenital papillary hidradenoma tumor cells of mutations in one or multiple genes that lead to the production of proteins that directly or indirectly stimulate the PI3K/AKT/mTOR intracellular signaling pathway. The mutated genes include PIK3CA, AKT1, PIK3CA, MAGI1, SYNE1, USP9X, KLNI (also termed CASC5), RNF213, FLCN, PDGFRB, AR (i.e. the androgen receptor gene), BTK, MLL3, KAT6A, BRD3, EP400, TET2, IL6, and IL7R. The PI3K/AKT/mTOR pathway promotes the grow (i.e. proliferation) and survival of cells and is abnormally activated in, and appears to contribute to the development and or progression of, a wide range of tumors. While further studies are needed, these findings suggest that the cited mutations lead to stimulation of the PI3K/AKT/mTOR pathway and thereby promote the development and/or progression of anogenital papillary hidradenoma in the majority of cases. These abnormalities have not yet been reported in ectopic papillary hidradenomas.

Diagnosis
The diagnosis of anogenital papillary hidradenoma lesions, while often suggested based on their clinical presentations, must be differentiated from a wide range of other similarly presenting anogenital lesions such as hemorrhoidal disease, anorectal abscesses, virus-related wart-like lesions, sebaceous cysts, mucous cysts, lipomas, neurofibromas, metastatic carcinomas with papillary histopathology, syringocystoadenocarcinoma papilliferum (i.e </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 Lown–Ganong–Levine syndrome and can you explain it in depth? [/INST] Lown–Ganong–Levine syndrome (LGL) is a pre-excitation syndrome of the heart. Those with LGL syndrome have episodes of abnormal heart racing with a short PR interval and normal QRS complexes seen on their electrocardiogram when in a normal sinus rhythm. LGL syndrome was originally thought to be due to an abnormal electrical connection between the atria and the ventricles, but is now thought to be due to accelerated conduction through the atrioventricular node in the majority of cases </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 Vossius ring and can you explain it in depth? [/INST]  </s>