On histologic examination, nasal polyps consist of hyperplastic edematous (excess fluid)  connective tissue  with some  seromucous glands  and cells representing inflammation (mostly  neutrophils  and  eosinophils ). Polyps have virtually no neurons. Therefore, the tissue that makes up the polyp does not have any tissue sensation and the polyp itself will not be painful. [ 6 ]  In early stages, the surface of the nasal polyp is covered by normal respiratory epithelium, but later it undergoes  metaplastic  change to squamous type epithelium with the constant irritation and inflammation. The submucosa shows large intercellular spaces filled with serous fluid. [ 15 ]


Other disorders can mimic the appearance of nasal polyps and should be considered if a mass is seen on exam. [ 16 ]  Examples include  encephalocele ,  glioma ,  inverted papilloma , and cancer. [ 10 ]  Early biopsy is recommended for unilateral nasal polyps to rule out more serious conditions such as cancer,  inverted papilloma , or  fungal sinusitis . [ 5 ]


The first line of treatment for nasal polyps is topical  steroids . [ 12 ]  Steroids decrease the inflammation of the sinus mucosa to decrease the size of the polyps and improve symptoms. [ 12 ]  Topical preparations are preferred in the form of a nasal spray but are often ineffective for people with many polyps. Steroids by mouth often provide drastic symptom relief, but should not be taken for long periods of time due to their side effects. Because steroids only shrink the size and swelling of the polyp, people often have recurrence of symptoms once the steroids are stopped. [ 12 ]  Decongestants do not shrink the polyps, but can decrease swelling and provide some relief. [ 7 ]  Antibiotics are only recommended if the person has a co-occurring  bacterial infection . [ 6 ]


In people with nasal polyps caused by aspirin or NSAIDs, avoidance of these medications will help with symptoms. Aspirin desensitization has also been shown to be beneficial. [ 12 ]


Endoscopic sinus surgery , advocated and popularized by Professor Stammberger, is often very effective for most people, providing rapid symptom relief. Endoscopic sinus surgery is minimally-invasive and is done entirely through the nostril with the help of a camera. Surgery should be considered for those with complete nasal obstruction, uncontrolled runny nose, nasal deformity caused by polyps or continued symptoms despite medical management. [ 7 ]  Surgery serves to remove the polyps as well as the surrounding inflamed mucosa, open obstructed nasal passages, and clear the sinuses. This not only removes the obstruction caused by the polyps themselves, but allows medications such as saline irrigations and topical steroids to become more effective. [ 19 ]  It has been suggested that one of the main objectives in sinus surgery for polyps is to allow delivery of the steroids into those areas of the sinuses where polyps develop, namely, the ethmoid sinuses. Specially designed long nozzles had been developed to use postoperatively to deliver steroids into those areas after sinus surgery for polyps. [ 20 ]


Surgery lasts approximately 45 to 60 minutes and can be done under general or local anesthesia. [ 19 ]  Most people tolerate the surgery without much pain, though this can vary from person to person. The person should expect some discomfort, congestion, and drainage from the nose in the first few days after surgery, but this should be mild. [ 21 ]  Complications from endoscopic sinus surgery are rare, but can include bleeding and damage to other structures in the area including the eye or brain. [ 21 ]


Many physicians recommend a course of oral steroids prior to surgery to reduce mucosal inflammation, decrease bleeding during surgery, and help with visualization of the polyps. [ 12 ]  Nasal steroid sprays should be used preventatively after surgery to delay or prevent recurrence. [ 7 ]  People often have recurrence of polyps even following surgery. Therefore, continued follow up with a combination of medical and surgical management is preferred for the treatment of nasal polyps. [ 12 ]


Nasal polyps resulting from chronic rhinosinusitis affect approximately 4.3% of the population. [ 6 ]  Nasal polyps occur more frequently in men than women and are more common as people get older, increasing drastically after the age of 40. [ 6 ]


Of people with chronic rhinosinusitis, 10% to 54% also have allergies. An estimated 40% to 80% of people with sensitivity to aspirin will develop nasal polyposis. [ 6 ]  In people with cystic fibrosis, nasal polyps are noted in 37% to 48%. [ 6 ]


The  nasal septum  ( Latin :  septum nasi ) separates the left and right airways of the  nasal cavity , dividing the two  nostrils .


It is  depressed  by the  depressor septi nasi muscle .


The fleshy external end of the nasal septum is called the  columella  or columella nasi, and is made up of  cartilage  and soft tissue. [ 2 ]  The nasal septum contains bone and  hyaline cartilage . [ 3 ]  It is normally about 2 mm thick. [ 4 ]


The nasal septum is composed of four structures:


The lowest part of the septum is a narrow strip of bone that projects from the maxilla and the  palatine bones , and is the length of the septum. This strip of bone is called the maxillary crest; it articulates in front with the septal nasal cartilage, and at the back with the vomer. [ 5 ]  The maxillary crest is described in the anatomy of the nasal septum as having a maxillary component and a palatine component.


At an early period, the septum of the nose consists of a plate of cartilage, known as the  ethmovomerine cartilage .


The posterosuperior part of this cartilage is  ossified  to form the perpendicular plate of the  ethmoid ; its anteroinferior portion persists as the septal cartilage, while the  vomer  is ossified in the membrane covering its posteroinferior part.


Two  ossification centers , one on either side of the middle line, appear about the eighth week of  fetal development  in this part of the membrane, and hence the vomer consists primarily of two lamellae.


About the third month, these unite below, and thus a deep groove is formed in which the cartilage is lodged.


As growth proceeds, the union of the lamellae extends upward and forward, and at the same time, the intervening plate of cartilage undergoes absorption.


By the onset of  puberty  the lamellae are almost completely united to form a median plate, but evidence of the bilaminar origin of the bone is seen in the everted alae of its upper border and in the groove on its anterior margin.


The nasal septum can depart from the centre line of the nose in a condition that is known as a  deviated septum  caused by trauma. However, it is normal to have a slight deviation to one side. The septum generally stays in the midline until about the age of seven, at which point it will frequently deviate to the right. An  operation  to straighten the nasal septum is known as a  septoplasty .


A  perforated nasal septum  can be caused by an  ulcer , trauma due to an inserted object, long-term exposure to  welding fumes , [ 6 ]  or  cocaine  use. There is a procedure that can be of help to those suffering from the perforated septum. A  silicone  button can be inserted in the hole to close the open sore.


The nasal septum can be affected by both  benign tumors  such as  fibromas , and  hemangiomas , and  malignant tumors  such as  squamous cell carcinoma .


A  nasal septum piercing  is usually carried out through the fleshy columella close to the end of the nasal septum.


Nasal septum deviation  is a physical disorder of the nose, involving a displacement of the  nasal septum . Some displacement is common, affecting 80% of people, mostly without their knowledge. [ 1 ]


The  nasal septum  is the bone and  cartilage  in the nose that separates the  nasal cavity  into the two  nostrils . The cartilage is called the  quadrangular cartilage  and the bones comprising the septum include the  maxillary crest ,  vomer , and the  perpendicular plate of the ethmoid . Normally, the septum lies centrally, and thus the nasal passages are symmetrical. [ 2 ]  A deviated septum is an abnormal condition in which the top of the cartilaginous ridge leans to the left or the right, causing obstruction of the affected nasal passage.


It is common for nasal septa to depart from the exact centerline; the septum is only considered deviated if the shift is substantial or causes problems. [ 3 ]  By itself, a deviated septum can go undetected for years and thus be without any need for correction. [ 3 ]


Symptoms of a deviated septum include infections of the  sinus  and  sleep apnea ,  snoring , repetitive  sneezing , facial pain,  nosebleeds ,  mouth breathing , difficulty with  breathing , mild to severe loss of the ability to  smell , [ 1 ] [ 4 ]  and possibly headaches. [ 5 ]  Only more severe cases of a deviated septum will cause symptoms of difficulty breathing and require treatment. [ 1 ]


It is most frequently caused by  impact trauma , such as by a blow to the face. [ 3 ]  It can also be a  congenital disorder , caused by compression of the nose during childbirth. [ 3 ]  Deviated septum is associated with genetic connective tissue disorders such as  Marfan syndrome ,  homocystinuria  and  Ehlers–Danlos syndrome . [ 6 ]


Nasal septum deviation is the most common cause of nasal obstruction. [ 7 ]  A history of trauma to the nose is often present including trauma from the process of birth or microfractures. [ 7 ]  A medical professional, such as an  otorhinolaryngologist  (ears, nose, and throat doctor), typically makes the diagnosis after taking a thorough history from the affected person and performing a physical examination. [ 7 ]  Imaging of the nose is sometimes used to aid in making the diagnosis as well. [ 7 ]


Medical therapy with nasal sprays including  decongestants ,  antihistamines , or nasal  corticosteroid  sprays is typically tried first before considering a surgical approach to correct nasal septum deviation. [ 7 ]  Medication temporarily relieves symptoms, but does not correct the underlying condition. Non-medical relief can also be obtained using  nasal strips .


A minor surgical procedure known as  septoplasty  can cure symptoms related to septal deviations. The surgery lasts roughly one hour and does not result in any cosmetic alteration or external scars. Nasal congestion, pain, [ 8 ]  drainage or swelling may occur within the first few days after the surgery. [ 9 ]  Recovery from the procedure may take anywhere from two days to four weeks to heal completely. [ citation needed ]  Septal bones never regrow. If symptoms reappear they are not related to deviations. Reappearance of symptoms may be due to  mucosal   metaplasia  of the nose. [ citation needed ]  There are times also when the surgery also may be unsuccessful, leading to a continuation of the symptoms.


A randomised controlled trial found that people who had septoplasty had a greater improvement in their symptoms and quality of life after 6 months than people who managed their nasal airway obstruction with nasal sprays. [ 10 ] [ 11 ]


The  nasociliary nerve  is a branch of the  ophthalmic nerve (CN V 1 )  (which is in turn a branch of the  trigeminal nerve (CN V) ). It is intermediate in size between the other two branches of the ophthalmic nerve, the  frontal nerve  and  lacrimal nerve . [ 1 ]


The nasociliary nerve enters the orbit via the superior orbital fissure, [ citation needed ]  through the  common tendinous ring , [ 1 ]  and between the two heads of the  lateral rectus muscle  and between the superior and inferior rami of the  oculomotor nerve . [ citation needed ]  It passes across the  optic nerve (CN II)  along with the  ophthalmic artery . It then runs obliquely beneath (inferior to) the  superior rectus muscle  and  superior oblique muscle  to the medial wall of the  orbital cavity  whereupon it emits the  posterior ethmoidal nerve , and the  anterior ethmoidal nerve . [ 1 ]


Branches of the nasociliary nerve include: [ 1 ]


The branches of the nasociliary nerve provide sensory innervation to structures surrounding the eye such as the cornea, eyelids, conjunctiva, ethmoid air cells and mucosa of the nasal cavity. [ citation needed ]


Since both the short and long ciliary nerves carry the afferent limb of the  corneal reflex , one can test the integrity of the nasociliary nerve (and, ultimately, the  trigeminal nerve ) by examining this reflex in the patient. Normally both eyes should blink when either cornea (not the conjunctiva, which is supplied by the adjacent cutaneous nerves) is irritated. If neither eye blinks, then either the ipsilateral nasociliary nerve is damaged, or the  facial nerve  (CN VII, which carries the efferent limb of this reflex) is bilaterally damaged. If only the contralateral eye blinks, then the ipsilateral facial nerve is damaged. If only the ipsilateral eye blinks, then the contralateral facial nerve is damaged. [ citation needed ]


The  neck dissection  is a  surgical procedure  for control of neck  lymph node   metastasis  from  squamous cell carcinoma  ( SCC ) of the head and neck. [ 1 ]  The aim of the procedure is to remove lymph nodes from one side of the neck into which cancer cells may have migrated.  Metastasis of squamous cell carcinoma into the lymph nodes of the neck reduce survival and is the most important factor in the spread of the disease. The metastases may originate from SCC of the upper aerodigestive tract, including the oral cavity, tongue,  nasopharynx ,  oropharynx ,  hypopharynx , and  larynx , as well as the  thyroid ,  parotid  and posterior scalp. [ citation needed ]


To describe the lymph nodes of the neck for neck dissection, the neck is divided into 6 areas called  Levels . The levels are identified by Roman numeral, increasing towards the chest. A further Level VII to denote lymph node groups in the superior  mediastinum  is no longer used. Instead, lymph nodes in other non-neck regions are referred to by the name of their specific nodal groups.


The 2001 revisions proposed by the American Head and Neck Society (AHNS) and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) are as follows.


The  nerve to the stapedius  is a branch of the  facial nerve (CN VII)  which innervates the  stapedius muscle . [ 1 ]  It arises from the CN VII within the  facial canal , [ 2 ]  opposite the  pyramidal eminence . It passes through a small canal in this eminence to reach the  stapedius muscle . [ 3 ]


Neurotology  or  neuro-otology  is a subspecialty of  otolaryngology—head and neck surgery , also known as ENT (ear, nose, and throat) medicine. [ 1 ]  Neuro-otology is closely related to  otology ,  clinical neurology [ 2 ]  and  neurosurgery .


Otology may refer to ENT  physicians  who "... [study] normal and pathological anatomy and physiology of the ear (hearing and vestibular sensory systems and related structures and functions) ...", and who treat diseases of the ear with medicine or surgery. [ 3 ]  In some instances, otology and neurotology are considered together—as so closely related that a clear demarcation between the subspecialties might not exist. For example, the  University of Maryland Medical Center  uses the term, "otologist/neurotologist". [ 4 ]


Otologists and neurotologists have specialized in otolaryngology and then further specialized in pathological conditions of the ear and related structures. Many general otolaryngologists are trained in otology or middle ear surgery, performing surgery such as a  tympanoplasty , or a reconstruction of the eardrum, when a hole remains from a prior ear tube or infection. Otologic surgery includes treatment of  conductive hearing loss  by reconstructing the hearing bones, or  ossicles , as a result of infection, or by replacing the stapes bone with a  stapedectomy  for  otosclerosis . Otology and neurotology encompass more complex surgery of the inner ear not typically performed by general otolaryngologists, such as removal of vestibular schwannoma,  cholesteatoma ,  labyrinthectomy , surgery of the  endolymphatic sac  for  Ménière's disease  and  cochlear implant  surgery.


It is more and more common in the United States as well as around the world for  otolaryngologists  to obtain additional advanced training in neurotology, which requires an additional one or two years of fellowship training after the usual five years of  residency .


Conditions treated by neurotologists include:


A  nosebleed , also known as  epistaxis , is an instance of  bleeding  from the  nose . [ 1 ]   Blood  can flow down into the stomach, and cause  nausea  and  vomiting . [ 8 ]  In more severe cases, blood may come out of both  nostrils . [ 9 ]  Rarely, bleeding may be so significant that  low blood pressure  occurs. [ 1 ]  Blood may also be forced to flow up and through the  nasolacrimal duct  and out of the eye, producing  bloody tears . [ 10 ]


Risk factors include trauma, including putting the finger in the nose,  blood thinners ,  high blood pressure ,  alcoholism ,  seasonal allergies , dry weather, and  inhaled corticosteroids . [ 3 ]  There are two types: anterior, which is more common; and posterior, which is less common but more serious. [ 3 ]  Anterior nosebleeds generally occur from  Kiesselbach's plexus  while posterior bleeds generally occur from the  sphenopalatine artery  or  Woodruff's plexus . [ 3 ]  The diagnosis is by direct observation. [ 1 ]


Prevention may include the use of  petroleum jelly  in the nose. [ 4 ]  Initially, treatment is generally the application of pressure for at least five minutes over the lower half of the nose. [ 5 ]  If this is not sufficient,  nasal packing  may be used. [ 5 ]   Tranexamic acid  may also be helpful. [ 6 ]  If bleeding episodes continue,  endoscopy  is recommended. [ 5 ]


About 60% of people have a nosebleed at some point in their life. [ 7 ]  About 10% of nosebleeds are serious. [ 7 ]  Nosebleeds are rarely fatal, accounting for only 4 of the 2.4 million deaths in the U.S. in 1999. [ 11 ]  Nosebleeds most commonly affect those younger than 10 and older than 50. [ 2 ]


Nosebleeds can occur due to a variety of reasons. Some of the most common causes include trauma from  nose picking , blunt trauma (such as a motor vehicle accident), or insertion of a foreign object (more likely in children). [ 4 ]  Low  relative humidity  (such as in centrally heated buildings),  respiratory tract infections ,  chronic sinusitis ,  rhinitis  or environmental  irritants  can cause inflammation and thinning of the tissue in the nose, leading to a greater likelihood of bleeding from the nose. [ 4 ]


Most causes of nose bleeding are self-limiting and do not require medical attention. However, if nosebleeds are recurrent or do not respond to home therapies, an underlying cause may need to be investigated. Some rarer causes are listed below: [ 2 ] [ 4 ] [ 12 ]


Coagulopathy


Dietary


Inflammatory


Medications/Drugs


Neoplastic


Traumatic


Vascular


The nasal  mucosa  contains a rich blood supply that can be easily ruptured and cause bleeding. Rupture may be spontaneous or initiated by trauma. Nosebleeds are reported in up to 60% of the population with peak incidences in those under the age of ten and over the age of 50 and appear to occur in males more than females. [ 15 ]  An increase in blood pressure (e.g. due to general hypertension) tends to increase the duration of spontaneous epistaxis. [ 16 ]   Anticoagulant  medication and disorders of blood clotting can promote and prolong bleeding. Spontaneous epistaxis is more common in the elderly as the nasal mucosa (lining) becomes dry and thin and blood pressure tends to be higher. The elderly are also more prone to prolonged nosebleeds as their blood vessels are less able to constrict and control the bleeding.


The vast majority of nosebleeds occur in the front  anterior  (front) part of the nose from the  nasal septum . This area is richly endowed with blood vessels ( Kiesselbach's plexus ). This region is also known as  Little's area . Bleeding farther back in the nose is known as a posterior bleed and is usually due to bleeding from  Woodruff's plexus , a venous plexus situated in the posterior part of inferior meatus. [ 17 ]  Posterior bleeds are often prolonged and difficult to control. They can be associated with bleeding from both nostrils and with a greater flow of blood into the mouth. [ 15 ]


Sometimes blood flowing from other sources of bleeding passes through the nasal cavity and exits the nostrils. It is thus blood coming from the nose but is not a true nosebleed, that is, not truly originating from the nasal cavity. Such bleeding is called "pseudoepistaxis" ( pseudo  +  epistaxis ). Examples include  blood coughed up  through the  airway  and ending up in the nasal cavity, then dripping out.


People with uncomplicated nosebleeds can use conservative methods to prevent future nosebleeds such as sleeping in a humidified environment or applying  petroleum jelly  to the nasal  nares . [ 4 ]


Individuals who suffer from nosebleeds regularly, especially children, are encouraged to use over-the-counter nasal saline sprays and avoid vigorous nose-blowing as preventative measures. [ 18 ]


Most anterior nosebleeds can be stopped by applying  direct pressure , which helps by promoting blood  clots . [ 4 ]  Those who have a nosebleed should first attempt to blow out any blood  clots  and then apply pressure to the soft anterior part of the nose (by pinching the  nasal ala ; not the bony  nasal bridge ) for at least five minutes and up to 30 minutes. [ 4 ]  Pressure should be firm and tilting the head forward helps decrease the chance of nausea and airway obstruction due to blood dripping into the airway. [ 15 ]  When attempting to stop a nosebleed at home, the head should not be tilted back. [ 2 ]  Swallowing excess blood can irritate the stomach and cause vomiting.  Vasoconstrictive  medications such as  oxymetazoline  (Afrin) or  phenylephrine  are widely available over the counter for treatment of  allergic rhinitis  and may also be used to control benign cases of epistaxis. [ 19 ]  For example, a few sprays of  oxymetazoline  may be applied into the bleeding side(s) of the nose followed by application of direct pressure. Those with nosebleeds that last longer than 30 minutes (despite use of direct pressure and vasoconstrictive medications such as  oxymetazoline ) should seek medical attention. [ 4 ]


This method involves applying a chemical such as  silver nitrate  to the nasal mucosa, which burns and seals off the bleeding. [ 12 ]  Eventually the nasal tissue to which the chemical is applied will undergo  necrosis . [ 12 ]  This form of treatment is best for mild bleeds, especially in children, that are clearly visible. [ 12 ]  A topical anesthetic (such as  lidocaine ) is usually applied prior to cauterization. Silver nitrate can cause blackening of the skin due to silver sulfide deposit, though this will fade with time. [ 20 ]  Once the  silver nitrate  is deposited,  saline  may be used to neutralize any excess  silver nitrate  via formation of  silver chloride  precipitate.


If pressure and chemical cauterization cannot stop bleeding, nasal packing is the mainstay of treatment. [ 21 ]  Nasal packing is typically categorized into anterior nasal packing and posterior nasal packing. [ 22 ]  Nasal packing may also be categorized into dissolvable and non-dissolvable types.


Dissolvable nasal packing materials stop bleeding through use of thrombotic agents that promote blood clots, such as  surgicel  and  gelfoam . [ 4 ]  The thrombogenic foams and gels do not require removal and dissolve after a few days. Typically, dissolvable nasal packing is first attempted; if the bleeding persists, non-dissolvable nasal packing is the next option.


Traditionally, nasal packing was accomplished by packing gauze into the nose, thereby placing pressure on the vessels in the nose and stopping the bleeding. Traditional gauze packing has been replaced with other non-dissolvable nasal packing products such as  Merocel  and the Rapid Rhino. [ 21 ]  The Merocel nasal tampon is similar to gauze packing except it is a synthetic foam polymer (made of polyvinyl alcohol and expands in the nose after application of water) that provides a less hospitable medium for bacteria. [ 4 ]  The Rapid Rhino stops nosebleeds using a balloon catheter, made of  carboxymethylcellulose , which has a cuff that is inflated by air to stop bleeding through extra pressure in the nasal cavity. [ 21 ]  Systematic review articles have demonstrated that the efficacy in stopping nosebleeds is similar between the Rapid Rhino and  Merocel  packs; however, the Rapid Rhino has been shown to have greater ease of insertion and reduced discomfort. [ 21 ]  Posterior nasal packing can be achieved by using a  Foley catheter , blowing up the balloon when it is in the back of the throat, and applying anterior traction so that the inflated balloon occludes the  choanae . [ 22 ]  Patients who receive non-dissolvable nasal packing need to return to a medical professional in 24–72 hours in order to have packing removed. [ 4 ] [ 3 ]  Complications of non-dissolvable nasal packing include  abscesses ,  septal hematomas ,  sinusitis , and pressure necrosis. [ 2 ]  In rare cases  toxic shock syndrome  can occur with prolonged nasal packing. As a result, any patient who has non-dissolvable nasal packing should be given prophylactic antibiotic medication to be taken as long as the nasal packing remains in the nose. [ 2 ]


Ongoing bleeding despite good nasal packing is a surgical emergency and can be treated by endoscopic evaluation of the nasal cavity under general anesthesia to identify an elusive bleeding point or to directly ligate (tie off) the blood vessels supplying the nose. These blood vessels include the  sphenopalatine , anterior and posterior ethmoidal arteries. More rarely the maxillary or a branch of the external  carotid artery  can be ligated. The bleeding can also be stopped by intra-arterial  embolization  using a catheter placed in the groin and threaded up the aorta to the bleeding vessel by an  interventional radiologist . [ 23 ]  There is no difference in outcomes between embolization and ligation as treatment options, but embolization is considerably more expensive. [ 24 ]  Continued bleeding may be an indication of more serious underlying conditions. [ 23 ]


Tranexamic acid  helps promote blood clotting. [ 6 ]  For nosebleeds it can be applied to the site of bleeding, taken by mouth, or injected into a vein. [ 6 ]


The utility of local cooling of the head and neck is controversial. [ 25 ]  Some state that applying ice to the nose or forehead is not useful. [ 26 ] [ 27 ]  Others feel that it may promote vasoconstriction of the nasal blood vessels and thus be useful. [ 28 ]  In Indonesian traditional medicine, betel leaf is used to stop nosebleeds as it contains tannin which causes blood to coagulate, thus stopping active bleeding. [ 29 ]


In the visual language of Japanese  manga  and  anime , nosebleeding often indicates that the bleeding person is sexually aroused. [ 30 ] [ 31 ] [ 32 ]  In  Western fiction , nosebleeds often signify intense mental focus or effort, particularly during the use of psychic powers. [ 33 ] [ 34 ]


In American and Canadian usage, " nosebleed section " and "nosebleed seats" are common slang for seating at sporting or other spectator events that are the highest up and farthest away from the event. The reference alludes to the propensity for nasal hemorrhage at high altitudes, usually owing to lower barometric pressure.


The oral history of the Native American  Sioux  tribe includes reference to women who experience nosebleeds as a result of a lover's playing of music, implying sexual arousal. [ 35 ]


In the  Finnish language , "picking blood from one's nose" and "begging for a nosebleed" are commonly used in abstract meaning to describe self-destructive behaviour, for example ignoring safety procedures or deliberately aggravating stronger parties. [ 36 ]


In  Filipino  slang, to "have a nosebleed" is to have serious difficulty conversing in English with a fluent or native English speaker. It can also refer to anxiety brought on by a stressful event such as an  examination  or a  job interview . [ 37 ]


In the  Dutch language , "pretending to have a nosebleed" is a saying that means pretending not to know anything about something. [ 38 ]


The word  epistaxis  is from  Ancient Greek :  ἐπιστάζω   epistazo , "to bleed from the nose" from  ἐπί   epi , "above, over" and  στάζω   stazo , "to drip [from the nostrils]". [ citation needed ]


A  nostril  (or  naris   / ˈ n ɛər ɪ s / ,  pl. :  nares   / ˈ n ɛər iː z / ) is either of the two  orifices  of the  nose . They enable the entry and exit of air and other gasses through the  nasal cavities .  In  birds  and  mammals , they contain branched bones or cartilages called  turbinates , whose function is to warm air on inhalation and remove moisture on exhalation.  Fish  do not breathe through noses, but they do have two small holes used for  smelling , which can also be referred to as nostrils (with the exception of  Cyclostomi , which have just one nostril).


In  humans , the  nasal cycle  is the normal  ultradian cycle  of each nostril's blood vessels becoming engorged in swelling, then shrinking.


The nostrils are separated by the  septum . The septum can sometimes be  deviated , causing one nostril to appear larger than the other.  With extreme damage to the septum and columella, the two nostrils are no longer separated and form a single larger external opening.


Like other  tetrapods , humans have two external nostrils (anterior nares) and two additional nostrils at the back of the nasal cavity, inside the head (posterior nares, posterior nasal apertures or  choanae ). They also connect the nose to the throat (the nasopharynx), aiding in respiration. Though all four nostrils were on the outside of the head of the aquatic ancestors of modern tetrapods, the nostrils for outgoing water (excurrent nostrils) migrated to the inside of the mouth, as evidenced by the discovery of  Kenichthys campbelli , a 395-million-year-old fossilized  lobe-finned fish  which shows this migration in progress. It has two nostrils between its front teeth, similar to human  embryos  at an early stage. If these fail to join up, the result is a  cleft palate . [ 1 ]


Each external nostril contains approximately 1,000 strands of  nasal hair , which function to filter foreign particles such as pollen and dust. [ 2 ]


It is possible for humans to smell different  olfactory  inputs in the two nostrils and experience a perceptual rivalry akin to that of  binocular rivalry  when there are two different inputs to the two eyes. [ 3 ]  Furthermore, scent information from the two nostrils leads to two types of neural activity [ 4 ]  with the first cycle corresponding to the ipsilateral and the second cycle corresponding to the contralateral odor representations.  In some cultures the extreme wide flaring of the nostrils accompanied by the baring of the upper teeth is often referred to as "doing the nostrils."


The  Procellariiformes  are distinguished from other birds by having tubular extensions of their nostrils.


Widely-spaced nostrils, like those of the  hammerhead shark , may be useful in determining the direction of an odour's source. [ 5 ] [ 6 ]


The  occipital artery  is a branch of the  external carotid artery  that provides arterial supply to the back of the scalp,  sternocleidomastoid  muscles, and deep muscles of the back and neck.


The occipital artery arises from (the posterior aspect of) the  external carotid artery  (some 2 cm distal to the origin of the external carotid artery). [ 1 ]


At its origin, the  hypoglossal nerve (CN XII)  crosses artery superficially as the nerve passes posteroanteriorly. [ 1 ]


The artery passes superoposteriorly deep to the posterior belly of the  digastricus muscle . It crosses the  internal carotid artery  and  vein , the  vagus nerve (CN X) ,  accessory nerve (CN XI) , and  hypoglossal nerve (CN XII) . [ 1 ]


It next ascends to the interval between the transverse process of the  atlas  and the  mastoid process  of the  temporal bone , and passes horizontally backward, grooving the surface of the latter bone, being covered by the  sternocleidomastoideus ,  splenius capitis ,  longissimus capitis , and  digastricus , and resting upon the  rectus capitis lateralis , the  obliquus superior , and  semispinalis capitis .


It then changes its course and runs vertically upward, pierces the fascia connecting the cranial attachment of the  trapezius  with the  sternocleidomastoideus , and ascends in a tortuous course in the superficial fascia of the scalp, where it divides into numerous branches, which reach as high as the  vertex of the skull  and  anastomose  with the  posterior auricular  and  superficial temporal  arteries.


Its terminal portion is accompanied by the  greater occipital nerve .


The  occipitalis muscle  ( occipital belly ) is a  muscle  which covers parts of the  skull . Some sources consider the occipital muscle to be a distinct muscle. However,  Terminologia Anatomica  currently classifies it as part of the  occipitofrontalis muscle  along with the  frontalis muscle .


The occipitalis muscle is thin and quadrilateral in form. It arises from tendinous fibers from the lateral two-thirds of the  superior nuchal line  of the  occipital bone  and from the  mastoid process  of the  temporal  and ends in the  epicranial aponeurosis . [ 1 ]


The occipitalis muscle is innervated by the  posterior auricular nerve  (a branch of the  facial nerve ) and its function is to move the  scalp  back. [ 2 ]  The muscles receives blood from the  occipital artery .


This article incorporates text in the  public domain  from  page 379  of the 20th edition of   Gray's Anatomy   (1918)


The  oculomotor nerve , also known as the  third cranial nerve ,  cranial nerve III , or simply  CN III ,  is a  cranial nerve  that enters the  orbit  through the  superior orbital fissure  and innervates  extraocular muscles  that enable most  movements of the eye  and that raise the eyelid.  The nerve also contains fibers that innervate the  intrinsic eye muscles  that enable pupillary constriction and accommodation (ability to focus on near objects as in reading). The oculomotor nerve is derived from the  basal plate  of the  embryonic   midbrain . Cranial nerves  IV  and  VI  also participate in control of  eye movement . [ 1 ]


The oculomotor nerve originates from the third nerve  nucleus  at the level of the  superior colliculus  in the midbrain. The third nerve nucleus is located ventral to the  cerebral aqueduct , on the pre-aqueductal  grey matter . The fibers from the two third nerve nuclei located laterally on either side of the cerebral aqueduct then pass through the  red nucleus . From the red nucleus fibers then pass via the  substantia nigra [ citation needed ]  to emerge from the substance of the brainstem at the oculomotor sulcus (a groove on the lateral wall of the  interpeduncular fossa ). [ 2 ]


On emerging from the  brainstem , the nerve is invested with a sheath of  pia mater , and enclosed in a prolongation from the  arachnoid . It passes between the  superior cerebellar  (below) and  posterior cerebral  arteries (above), and then pierces the dura mater anterior and lateral to the  posterior clinoid process , passing between the free and attached borders of the  tentorium cerebelli . [ citation needed ]


It traverses the  cavernous sinus , above the other orbital nerves receiving in its course one or two filaments from the  cavernous plexus  of the sympathetic nervous system, and a communicating branch from the  ophthalmic division  of the  trigeminal  nerve. As the oculomotor nerve enters the orbit via the  superior orbital fissure  it then divides into a superior and an inferior branch. [ 1 ]


The  superior branch  of the oculomotor nerve or the  superior division , the smaller, passes medially over the  optic nerve . It supplies the  superior rectus  and  levator palpebrae superioris .


The  inferior branch  of the oculomotor nerve or the  inferior division , the larger, divides into three branches.


All these branches enter the muscles on their ocular surfaces, with the exception of the nerve to the inferior oblique, which enters the muscle at its posterior border.


The oculomotor nerve (CN III) arises from the anterior aspect of the  mesencephalon  (midbrain). There are two nuclei for the oculomotor nerve:


Sympathetic postganglionic fibres also join the nerve from the plexus on the internal carotid artery in the wall of the cavernous sinus and are distributed through the nerve, e.g., to the smooth muscle of superior tarsal (Mueller's) muscle.


The oculomotor nerve includes axons of type GSE,  general somatic efferent , which innervate skeletal muscle of the levator palpebrae superioris, superior rectus, medial rectus, inferior rectus, and inferior oblique muscles. (Innervates all the extrinsic muscles except superior oblique and lateral rectus.)


The nerve also includes axons of type GVE,  general visceral efferent , which provide preganglionic parasympathetics to the ciliary ganglion. From the ciliary ganglion postganglionic fibers pass through the short ciliary nerve to the constrictor pupillae of the iris and the ciliary muscles.


Paralysis of the oculomotor nerve, i.e.,  oculomotor nerve palsy , can arise due to:


In people with  diabetes  and older than 50 years of age, an oculomotor nerve palsy, in the classical sense, occurs with sparing (or preservation) of the pupillary reflex.  This is thought to arise due to the anatomical arrangement of the  nerve fibers  in the oculomotor nerve; fibers controlling the pupillary function are superficial and spared from  ischemic  injuries typical of diabetes.  On the converse, an aneurysm which leads to compression of the oculomotor nerve affects the superficial fibers and manifests as a third nerve palsy with loss of the pupillary reflex (in fact, this third nerve finding is considered to represent an aneurysm—until proven otherwise—and should be investigated). [ 3 ]


Cranial nerves III, IV, and VI are usually tested together as part of the  cranial nerve examination . The examiner typically instructs the patient to hold his head still and follow only with the eyes a finger or penlight that circumscribes a large "H" in front of the patient. By observing the  eye movement  and  eyelids , the examiner is able to obtain more information about the  extraocular muscles , the  levator palpebrae superioris muscle , and cranial nerves III, IV, and VI. Loss of function of any of the eye muscles results in  ophthalmoparesis .


Since the oculomotor nerve controls most of the eye muscles, it may be easier to detect damage to it.  Damage to this nerve, termed  oculomotor nerve palsy , is known by its  down and out  symptoms, because of the position of the affected eye (lateral, downward deviation of gaze).


The oculomotor nerve also controls the constriction of the  pupils  and thickening of the lens of the eye. This can be tested in two main ways. By moving a finger toward a person's face to induce  accommodation , their pupils should constrict.


Shining a light into one eye should result in equal constriction of the other eye. Fibers from the optic nerves  cross over  in the optic chiasm with some fibers passing to the contralateral optic nerve tract. This is the basis of the " swinging-flashlight test ".


Loss of  accommodation  and continued pupillary dilation can indicate the presence of a lesion on the oculomotor nerve.


This article incorporates text in the  public domain  from  page 884  of the 20th edition of   Gray's Anatomy   (1918)


The  olfactory bulb  ( Latin :  bulbus olfactorius ) is a  neural structure  of the  vertebrate   forebrain  involved in  olfaction , the sense of  smell . It sends olfactory information to be further processed in the  amygdala , the  orbitofrontal cortex  (OFC) and the  hippocampus  where it plays a role in emotion, memory and learning.


The bulb is divided into two distinct structures: the main olfactory bulb and the accessory olfactory bulb. The main olfactory bulb connects to the amygdala via the  piriform cortex  of the  primary olfactory cortex  and directly projects from the main olfactory bulb to specific amygdala areas. The accessory olfactory bulb resides on the dorsal-posterior region of the main olfactory bulb and forms a parallel pathway.


Destruction of the olfactory bulb results in  ipsilateral   anosmia , while irritative  lesions  of the  uncus  can result in olfactory and  gustatory  hallucinations.


In most vertebrates, the olfactory bulb is the most  rostral  (forward) part of the brain, as seen in rats. In humans, however, the olfactory bulb is on the  inferior  (bottom) side of the brain. The olfactory bulb is supported and protected by the  cribriform plate  of the  ethmoid bone , which in mammals separates it from the  olfactory epithelium , and which is perforated by  olfactory nerve  axons. The bulb is divided into two distinct structures: the main olfactory bulb and the accessory olfactory bulb.


The main olfactory bulb has a multi-layered  cellular architecture . In order from surface to the center the layers are:


The olfactory bulb transmits smell information from the nose to the brain, and is thus necessary for a proper sense of smell. As a  neural circuit , the glomerular layer receives direct input from  afferent nerves , made up of the axons from approximately ten million  olfactory receptor neurons  in the  olfactory mucosa , a region of the  nasal cavity . The ends of the axons cluster in spherical structures known as  glomeruli  such that each glomerulus receives input primarily from olfactory receptor neurons that express the same  olfactory receptor . The glomeruli layer of the olfactory bulb is the first level of  synaptic processing . [ 1 ]


The glomeruli layer represents a spatial odor map organized by chemical structure of  odorants  like  functional group  and carbon chain length.  This spatial map is divided into zones and clusters, which represent similar glomeruli and therefore similar odors.  One cluster in particular is associated with rank, spoiled smells which are represented by certain chemical characteristics.  This classification may be evolutionary to help identify food that is no longer good to eat. The spatial map of the glomeruli layer may be used for perception of odor in the olfactory cortex. [ 2 ]


The next level of synaptic processing in the olfactory bulb occurs in the external plexiform layer, between the glomerular layer and the mitral cell layer.  The external plexiform layer contains  astrocytes ,  interneurons  and some mitral cells.  It does not contain many  cell bodies , rather mostly  dendrites  of mitral cells and GABAergic granule cells  [ 3 ]  are also permeated by dendrites from neurons called  mitral cells , which in turn output to the  olfactory cortex . Numerous interneuron types exist in the olfactory bulb including  periglomerular cells  which synapse within and between glomeruli, and granule cells which synapse with mitral cells.  The granule cell layer is the deepest layer in the olfactory bulb.  It is made up of dendrodendritic granule cells that synapse to the mitral cell layer. [ 4 ]


This part of the brain receives sensations of smell.
As a neural circuit, the olfactory bulb has one source of sensory input (axons from olfactory receptor neurons of the olfactory epithelium), and one output (mitral cell axons).  As a result, it is generally assumed that it functions as a  filter , as opposed to an associative circuit that has many inputs and many outputs. However, the olfactory bulb also receives "top-down" information from such brain areas as the  olfactory cortex ,   amygdala ,  neocortex ,  hippocampus ,  locus coeruleus , and  substantia nigra . [ 5 ]
Its potential functions can be placed into four non-exclusive categories: [ citation needed ]


While all of these functions could theoretically arise from the olfactory bulb's circuit layout, it is unclear which, if any, of these functions are performed exclusively by the olfactory bulb. By analogy to similar parts of the brain such as the  retina , many researchers have focused on how the olfactory bulb filters incoming information from receptor neurons in space, or how it filters incoming information in time.  At the core of these proposed filters are the two classes of interneurons; the periglomerular cells, and the granule cells.  Processing occurs at each level of the main olfactory bulb, beginning with the spatial maps that categorize odors in the glomeruli layer. [ 2 ]


Interneurons in the external plexiform layer are responsive to pre-synaptic action potentials and exhibit both  excitatory postsynaptic potentials  and  inhibitory postsynaptic potentials .  Neural firing varies temporally, there are periods of fast, spontaneous firing and slow modulation of firing.  These patterns may be related to sniffing or change in intensity and concentration of odorant. [ 3 ]  Temporal patterns may have effect in later processing of spatial awareness of odorant. [ citation needed ]  For example, synchronized mitral cell spike trains appear to help to discriminate similar odors better than when those spike trains are not synchronized. [ 6 ]  A well known model [ 7 ]  is that the bulbar neural circuit transforms the odor information in the receptors to a population pattern of neural oscillatory activities [ 8 ]  in the mitral cell population, [ 7 ]  and this pattern is then recognized by the associative memories of olfactory objects in the olfactory cortex. [ 9 ] [ 10 ]  Top-down feedback from the olfactory cortex to the olfactory bulb modulates the bulbar responses, so that, for example, the bulb can adapt to a pre-existing olfactory background to single out a foreground odor from an odor mixture for recognition, [ 10 ] [ 11 ]  or can enhance sensitivity to a target odor during odor search. [ 12 ] [ 10 ]   Destruction to the olfactory bulb results in  ipsilateral   anosmia  while irritative  lesion  of the  uncus  can result in olfactory and  gustatory  hallucinations. [ citation needed ]


The interneurons in the external plexiform layer perform feedback inhibition on the mitral cells to control  back propagation .  They also participate in  lateral inhibition  of the mitral cells. This inhibition is an important part of olfaction as it aids in odor discrimination by decreasing firing in response to background odors and differentiating the responses of olfactory nerve inputs in the mitral cell layer. [ 1 ]   Inhibition of the mitral cell layer by the other layers contributes to odor discrimination and higher level processing by modulating the output from the olfactory bulb.  These hyperpolarizations during odor stimulation shape the responses of the mitral cells to make them more specific to an odor. [ 4 ]


There is a lack of information regarding the function of the internal plexiform layer which lies between the mitral cell layer and the granule cell layer. [ citation needed ]


The basal  dendrites  of  mitral cells  are connected to interneurons known as  granule cells , which by some theories produce  lateral inhibition  between mitral cells.  The synapse between mitral and granule cells is of a rare class of synapses that are "dendro-dendritic" which means that both sides of the synapse are dendrites that release neurotransmitter.  In this specific case, mitral cells release the excitatory neurotransmitter  glutamate , and granule cells release the inhibitory neurotransmitter  Gamma-aminobutyric acid  (GABA).  As a result of its bi-directionality, the dendro-dendritic synapse can cause mitral cells to inhibit themselves (auto-inhibition), as well as neighboring mitral cells (lateral inhibition).  More specifically, the granule cell layer receives excitatory glutamate signals from the basal dendrites of the mitral and tufted cells.  The granule cell in turn releases GABA to cause an inhibitory effect on the mitral cell.  More neurotransmitter is released from the activated mitral cell to the connected dendrite of the granule cell, making the inhibitory effect from the granule cell to the activated mitral cell stronger than the surrounding mitral cells. [ 4 ]   It is not clear what the functional role of lateral inhibition would be, though it may be involved in boosting the signal-to-noise ratio of odor signals by silencing the basal firing rate of surrounding non-activated neurons.  This in turn aids in odor discrimination. [ 1 ]   Other research suggest that the lateral inhibition contributes to differentiated odor responses, which aids in the processing and perception of distinct odors. [ 4 ]  There is also evidence of cholinergic effects on granule cells that enhance depolarization of granule cells making them more excitable which in turn increases inhibition of mitral cells.  This may contribute to a more specific output from the olfactory bulb that would closer resemble the glomerular odor map. [ 13 ] [ 14 ]
Olfaction is distinct from the other  sensory systems  where peripheral  sensory receptors  have a relay in the  diencephalon . Therefore, the olfactory bulb plays this role for the   olfactory system .


In vertebrates, the accessory olfactory bulb (AOB), which resides on the dorsal-posterior region of the main olfactory bulb, forms a parallel pathway independent from the main olfactory bulb. The  vomeronasal organ  sends projections to the accessory olfactory bulb [ 15 ] [ 16 ]  making it the second processing stage of the  accessory olfactory system . As in the main olfactory bulb, axonal input to the accessory olfactory bulb forms synapses with mitral cells within glomeruli. The accessory olfactory bulb receives axonal input from the  vomeronasal organ , a distinct sensory epithelium from the main  olfactory epithelium  that detects chemical stimuli relevant for social and reproductive behaviors, but probably also generic odorants. [ 17 ]  It has been hypothesized that, in order for the vomernasal pump to turn on, the main olfactory epithelium must first detect the appropriate odor. [ 18 ]  However, the possibility that the vomeronasal system works in parallel or independently from generic olfactory inputs has not been ruled out yet.


Vomeronasal sensory neurons provide direct excitatory inputs to AOB principle neurons called mitral cells [ 19 ]  which are transmitted to the  amygdala  and  hypothalamus  and therefore are directly involved in sex hormone activity and may influence aggressiveness and mating behavior. [ 20 ]  Axons of the vomeronasal sensory neurons express a given receptor type which, differently from what occurs in the main olfactory bulb, diverge between 6 and 30 AOB glomeruli. Mitral cell dendritic endings go through a dramatic period of targeting and clustering just after presynaptic unification of the sensory neuron axons. The connectivity of the vomernasal sensorglomery neurons to mitral cells is precise, with mitral cell dendrites targeting the  glomeruli . [ 19 ]  There is evidence against the presence of a functional accessory olfactory bulb in humans and other higher primates. [ 21 ]


The AOB is divided into two main subregions, anterior and posterior, which receive segregated synaptic inputs from two main categories of vomeronasal sensory neurons, V1R and V2R, respectively. This appears as a clear functional specialization, given the differential role of the two populations of sensory neurons in detecting chemical stimuli of different type and molecular weight. Although it doesn't seem to be maintained centrally, where mitral cell projections from both sides of the AOB converge. A clear difference of the AOB circuitry, compared to the rest of the bulb, is its heterogeneous connectivity between mitral cells and vomeronasal sensory afferents within neuropil glomeruli. AOB mitral cells indeed contact through apical dendritic processes glomeruli formed by afferents of different receptor neurons, thus breaking the one-receptor-one-neuron rule which generally holds for the main olfactory system. This implies that stimuli sensed through the VNO and elaborated in the AOB are subjected to a different and probably more complex level of elaboration. Accordingly, AOB mitral cells show clearly different firing patterns compared to other bulbar projection neurons. [ 22 ]  Additionally, top down input to the olfactory bulb differentially affects olfactory outputs. [ 23 ]


The olfactory bulb sends olfactory information to be further processed in the  amygdala , the  orbitofrontal cortex  (OFC) and the  hippocampus  where it plays a role in emotion, memory and learning.  The main olfactory bulb connects to the amygdala via the  piriform cortex  of the  primary olfactory cortex  and directly projects from the main olfactory bulb to specific amygdala areas. [ 24 ]  The amygdala passes olfactory information on to the  hippocampus .  The orbitofrontal cortex, amygdala, hippocampus,  thalamus , and olfactory bulb have many interconnections directly and indirectly through the cortices of the primary olfactory cortex.  These connections are indicative of the association between the olfactory bulb and higher areas of processing, specifically those related to emotion and memory. [ 24 ]


Associative learning  between odors and behavioral responses takes place in the  amygdala .  The odors serve as the reinforcers or the punishers during the associative learning process; odors that occur with positive states reinforce the behavior that resulted in the positive state while odors that occur with negative states do the opposite. Odor cues are coded by neurons in the amygdala with the behavioral effect or emotion that they produce.  In this way odors reflect certain emotions or physiological states. [ 25 ]  Odors become associated with pleasant and unpleasant responses, and eventually the odor becomes a cue and can cause an emotional response.  These odor associations contribute to emotional states such as fear.  Brain imaging shows amygdala activation correlated with pleasant and unpleasant odors, reflecting the association between odors and emotions. [ 25 ]


The  hippocampus  aids in olfactory memory and learning as well.  Several olfaction-memory processes occur in the hippocampus.  Similar to the process in the amygdala, an odor is associated with a particular reward, i.e. the smell of food with receiving sustenance. [ 26 ]   Odor in the hippocampus also contributes to the formation of  episodic memory ; the memories of events at a specific place or time.  The time at which certain neurons fire in the hippocampus is associated by neurons with a stimulus such as an odor.  Presentation of the odor at a different time may cause recall of the memory, therefore odor aids in recall of episodic memories. [ 26 ]


In lower vertebrates (lampreys and teleost fishes), mitral cell (principal olfactory neurons) axons project exclusively to the right hemisphere of Habenula in an asymmetric manner. It is reported that dorsal Habenula (Hb) are functional asymmetric with predominant odor responses in right hemisphere. It was also shown that Hb neurons are spontaneous active even in absence of olfactory stimulation. These spontaneous active Hb neurons are organized into functional clusters which were proposed to govern olfactory responses. (Jetti, SK. et al. 2014, Current Biology)


Further evidence of the link between the olfactory bulb and emotion and memory is shown through  animal depression models . Olfactory bulb removal in rats effectively causes structural changes in the amygdala and hippocampus and behavioral changes similar to that of a person with depression. Researchers use rats with olfactory bulbectomies to research antidepressants. [ 27 ]  Research has shown that removal of the olfactory bulb in rats leads to  dendrite  reorganization, disrupted cell growth in the hippocampus, and decreased  neuroplasticity  in the hippocampus. These hippocampal changes due to olfactory bulb removal are associated with behavioral changes characteristic of depression, demonstrating the correlation between the olfactory bulb and emotion. [ 28 ]  The hippocampus and amygdala affect odor perception. During certain physiological states such as hunger a food odor may seem more pleasant and rewarding due to the associations in the amygdala and hippocampus of the food odor stimulus with the reward of eating. [ 25 ]


Olfactory information is sent to the primary olfactory cortex, where projections are sent to the  orbitofrontal cortex . The OFC contributes to this odor-reward association as well as it assesses the value of a reward, i.e. the nutritional value of a food.  The OFC receives projections from the  piriform cortex , amygdala, and parahippocampal cortices. [ 25 ]  Neurons in the OFC that encode food reward information activate the reward system when stimulated, associating the act of eating with reward.  The OFC further projects to the  anterior cingulate cortex  where it plays a role in appetite. [ 29 ]   The OFC also associates odors with other stimuli, such as taste. [ 25 ]  Odor perception and discrimination also involve the OFC.  The spatial odor map in the glomeruli layer of the olfactory bulb may contribute to these functions.  The odor map begins processing of olfactory information by spatially organizing the glomeruli.  This organizing aids the olfactory cortices in its functions of perceiving and discriminating odors. [ 2 ]


The olfactory bulb is, along with both the  subventricular zone  and the subgranular zone of the dentate gyrus of the hippocampus, one of only three structures in the brain observed to undergo continuing  neurogenesis  in adult mammals. [ citation needed ]  In most mammals, new neurons are born from neural stem cells in the sub-ventricular zone and migrate rostrally towards the main  [ 30 ]  and accessory [ 31 ]    olfactory bulbs. Within the olfactory bulb these immature neuroblasts develop into fully functional granule cell interneurons and periglomerular cell interneurons that reside in the granule cell layer and glomerular layers, respectively.  The olfactory sensory neuron axons that form synapses in olfactory bulb glomeruli are also capable of regeneration following regrowth of an olfactory sensory neuron residing in the olfactory epithelium.  Despite dynamic turnover of sensory axons and interneurons, the projection neurons (mitral and tufted neurons) that form synapses with these axons are not structurally plastic. [ citation needed ]


The function of adult neurogenesis in this region remains a matter of study.  The survival of immature neurons as they enter the circuit is highly sensitive to olfactory activity and in particular associative learning tasks.  This has led to the hypothesis that new neurons participate in learning processes. [ 32 ]   No definitive behavioral effect has been observed in loss-of-function experiments suggesting that the function of this process, if at all related to olfactory processing, may be subtle. [ citation needed ]


The olfactory lobe is a structure of the vertebrate forebrain involved in olfaction, or sense of smell. Destruction of the olfactory bulb results in ipsilateral  anosmia .


Comparing the structure of the olfactory bulb among vertebrate species, such as the  leopard frog  and the  lab mouse , reveals that they all share the same fundamental layout (five layers containing the nuclei of three major cell types; see "Anatomy" for details), despite being dissimilar in shape and size.  A similar structure is shared by the analogous olfactory center in the fruit fly  Drosophila melanogaster , the  antennal lobe .  One possibility is that vertebrate olfactory bulb and insect antennal lobe structure may be similar because they contain an optimal solution to a  computational problem  experienced by all olfactory systems and thus may have evolved independently in different phyla – a phenomenon generally known as  convergent evolution . [ 33 ] [ 34 ]


"The increase of brain size relative to body size— encephalization —is intimately linked with human evolution. However, two genetically different evolutionary lineages,  Neanderthals  and  modern humans , have produced similarly large-brained human species. Thus, understanding human brain evolution should include research into specific cerebral reorganization, possibly reflected by brain shape changes. Here we exploit developmental integration between the brain and its underlying skeletal base to test hypotheses about brain evolution in  Homo . Three-dimensional geometric morphometric analyses of endobasicranial shape reveal previously undocumented details of evolutionary changes in  Homo sapiens . Larger olfactory bulbs, relatively wider orbitofrontal cortex, relatively increased and forward projecting temporal lobe poles appear unique to modern humans. Such brain reorganization, beside physical consequences for overall skull shape, might have contributed to the evolution of  H. sapiens'  learning and social capacities, in which higher olfactory functions and its cognitive, neurological behavioral implications could have been hitherto underestimated factors." [ 35 ]


The  olfactory epithelium  is a specialized  epithelial  tissue inside the  nasal cavity  that is involved in  smell . In humans, it measures
5 cm 2  (0.78 sq in) [ 1 ]  and lies on the roof of the nasal cavity about 7 cm (2.8 in) above and behind the nostrils. [ 2 ]  The olfactory epithelium is the part of the  olfactory system  directly responsible for detecting  odors .


Olfactory epithelium consists of four distinct cell types: [ 3 ]


The  olfactory receptor neurons  are sensory neurons of the olfactory epithelium. They are  bipolar neurons  and their apical poles express odorant receptors on  non-motile cilia  at the ends of the  dendritic knob ,  [ 4 ]  which extend out into the airspace to interact with odorants. Odorant receptors bind odorants in the airspace, which are made soluble by the serous secretions from  olfactory glands  located in the lamina propria of the mucosa. [ 5 ]  The axons of the olfactory sensory neurons congregate to form the  olfactory nerve  (CN I). Once the axons pass through the  cribriform plate , they terminate and synapse with the dendrites of  mitral cells  in the  glomeruli  of the  olfactory bulb .


Analogous to neural  glial cells , the supporting cells are non-neural cells in the olfactory epithelium that are located in the apical layer of the pseudostratified ciliated columnar epithelium. There are two types of supporting cells in the olfactory epithelium:  sustentacular cells  and microvillar cells. The sustentacular cells function as metabolic and physical support for the olfactory epithelium. Microvillar cells are another class of supporting cells that are morphologically and biochemically distinct from the sustentacular cells, and arise from a basal cell population that expresses the  c-KIT  cell surface protein. [ 6 ]


Resting on or near the  basal lamina  of the olfactory epithelium, basal cells are stem cells capable of division and differentiation into either supporting or olfactory cells.  While some of these basal cells divide rapidly, a significant proportion remain relatively quiescent and replenish olfactory epithelial cells as needed. This leads to the olfactory epithelium being replaced every 6–8 weeks. [ 7 ]


Basal cells  can be divided on the basis of their cellular and histological features into two populations: the horizontal basal cells, which are slowly dividing reserve cells that express p63; and globose basal cells, which are a heterogeneous population of cells consisting of reserve cells, amplifying progenitor cells, and immediate precursor cells. [ 8 ]


A  brush cell  is a microvilli-bearing columnar cell with its basal surface in contact with afferent nerve endings of the  trigeminal nerve  (CN V) and is specialized for transduction of general sensation.


Tubuloalveolar serous secreting glands lying in the lamina propria of the  olfactory mucosa .  These glands deliver a proteinaceous secretion via ducts onto the surface of the mucosa.  The role of the secretions are to trap and dissolve odiferous substances for the bipolar neurons.  Constant flow from the olfactory glands allows old odors to be constantly washed away. [ 5 ]


The olfactory epithelium derives from two structures during  embryonic development : the  nasal placodes , which were long believed to be its sole origin; and  neural crest cells , whose contributions have been identified more recently through  fate mapping  studies. [ 9 ]


The embryonic olfactory epithelium consists of fewer cell types than in the adult, including apical and basal  progenitor cells , as well as immature  olfactory sensory neurons . [ 9 ]  Early embryonic neurogenesis relies mostly on the apical cells, while later stage embryonic  neurogenesis  and secondary neurogenesis in adults relies on basal stem cells. [ 10 ]   The  axons  of the immature  olfactory sensory neurons , along with a mixed population of  migratory cells , including immature  olfactory ensheathing cells  and  gonadotropin-releasing hormone neurons  form a "migratory mass" that travels towards the  olfactory bulb . [ 9 ] [ 10 ]  At the end of the embryonic stage, the epithelium develops into a  pseudostratified columnar epithelium  and begins secondary neurogenesis. [ 9 ]


Neurogenic placodes  are transient, focal aggregations of  ectoderm  located in the developmental region of the future  vertebrate   head , and give rise to  sensory organs . [ 11 ]  Early cranial sensory placodes are marked by expression of  Six1 , part of the Six family of transcription factors that regulate the  preplacodal  specification. [ 12 ]  The  olfactory placode  forms as two thickenings of non-neural region of  embryonic ectoderm . [ 13 ]  In mice, the olfactory placode derives from an anterior portion of the  neural tube , ~9-9.5 days into development and not long after the closure of the  neural plate . [ 9 ]  Development of the olfactory placode requires the presence underlying  neural crest -derived  mesenchymal  tissue. [ 12 ]  The specification of the olfactory placode tissue involves signaling of multiple  gene networks , beginning with signals from  bone morphogenetic proteins  (BMP),  retinoic acid  (RA), and  fibroblast growth factor  (FGF), specifically  FGF8 . [ 14 ]  The resulting regulated downstream expression of  transcription factors , such as  Pax6 ,  Dlx3 ,  Sox2 , and others, within the presumptive olfactory placode are crucial for sub-regionalization within the future olfactory epithelium and is responsible for the diversity of cells that compose the future epithelium. [ 9 ] [ 12 ] [ 15 ]


Similar to the other embryonic placodes, the olfactory placode gives rise to both neural and non-neural structures, ultimately resulting in the formation of the nasal epithelium. [ 16 ]  The specification of neural versus non-neural tissue involves signals both within the olfactory placode, and between the olfactory placode and the underlying  mesenchymal  compartment. [ 12 ]  Continued signaling by BMP, FGF, and RA, the  morphogens  that initially induced placode formation, collectively coordinate the patterning of olfactory placode tissue into the future distinct cell types that make up the olfactory epithelium. [ 16 ]  The cell types derived from the olfactory placode include: [ 17 ]


However, there is significant evidence for an additional  neural crest -origin for many of these cell types as well. [ 13 ]


Olfaction  results from the proper development and interaction of the two components of the primary  olfactory pathway : the olfactory epithelium and the  olfactory bulb . [ 18 ]  The olfactory epithelium contains  olfactory sensory neurons , whose  axons   innervate  the olfactory bulb. In order for olfactory sensory neurons to function properly, they must express  odorant receptors  and the proper  transduction proteins  on  non-motile cilia  that extend from the  dendritic knob  in addition to projecting their axons to the olfactory bulb. [ 19 ]


The cells of the olfactory epithelium, including olfactory sensory neurons, begin to  differentiate  soon after the induction of the  olfactory placode . Once the olfactory sensory neurons differentiate, they express odorant receptors, which transduce  odorant  information from the environment to the  central nervous system  and aids in the development of the odorant map. [ 20 ]  The differentiated olfactory sensory neurons extend  pioneering axons , which follow  guidance cues  released by the underlying  mesenchyme , as well as other  chemotrophic cues  released from the  telencephalon . [ 10 ]  As development of the olfactory pathway progresses, more axons innervate the olfactory bulb, which develops from the rostral-most region of telencephalon. The organization and subsequent processing of odorant information is possible due to the convergence of olfactory sensory neuron axons expressing the same odorant receptors onto the same  glomerulus  at the olfactory bulb. [ 21 ]


The olfactory epithelium can be damaged by inhalation of toxic fumes, physical injury to the interior of the nose, and possibly by the use of some nasal sprays.  Because of its regenerative capacity, damage to the olfactory epithelium can be temporary but in extreme cases, injury can be permanent, leading to  anosmia .


The  olfactory nerve ,  also known as the  first cranial nerve ,  cranial nerve I , or simply  CN I , is a  cranial nerve  that contains sensory nerve fibers relating to  the sense of smell .


The  afferent nerve fibers  of the  olfactory receptor neurons  transmit  nerve impulses  about  odors  to the  central nervous system  ( olfaction ). Derived from the  embryonic   nasal placode , the olfactory nerve is somewhat unusual among cranial nerves because it is capable of some regeneration if damaged. The olfactory nerve is sensory in nature and originates on the  olfactory mucosa  in the upper part of the  nasal cavity . [ 1 ]  From the olfactory mucosa, the nerve (actually many small nerve fascicles) travels up through the  cribriform plate  of the  ethmoid bone  to reach the surface of the brain. Here the fascicles enter the  olfactory bulb  and synapse there; from the bulbs (one on each side) the olfactory information is transmitted into the brain via the  olfactory tract . [ 2 ]  The fascicles of the olfactory nerve are not visible on a cadaver brain because they are severed upon removal. [ 3 ]   : 548


The specialized  olfactory receptor neurons  of the olfactory nerve are located in the olfactory  mucosa  of the upper parts of the  nasal cavity . The olfactory nerves consist of a collection of many sensory nerve fibers that extend from the olfactory epithelium to the  olfactory bulb , passing through the many openings of the  cribriform plate , a  sieve -like structure of the  ethmoid bone .


The sense of  smell  arises from the stimulation of  receptors  by small molecules in inspired air of varying spatial, chemical, and electrical properties that reach the nasal epithelium in the nasal cavity during inhalation. These stimulants are transduced into electrical activity in the olfactory neurons, which then transmit these impulses to the olfactory bulb and from there they reach the olfactory areas of the brain via the  olfactory tract .


The olfactory nerve is the shortest of the twelve cranial nerves and, similar to the optic nerve, does not emanate from the  brainstem . [ 2 ]


The olfaction system works to ensure that people can successfully identify an extensive range of odorants and distinguish odors from one another. [ 4 ] [ 5 ]  Odorants interact with the  olfactory receptor neurons (ORNs)  at the periphery and transmit olfactory information to the  central nervous system  via  axons  at the basal surface. [ 4 ] [ 5 ]  These axons aggregate, forming the olfactory nerve. [ 4 ] [ 5 ] [ 6 ]  Therefore, the olfactory nerve works to transduce  sensory stimuli  in the form of odorants and encode them into electrical signals, which are relayed to higher-order centers through  synaptic transmission . [ 4 ] [ 6 ]


Odorants bind to specific  odorant receptor proteins  contained to the outer surface of  olfactory cilia  within the  olfactory epithelium . [ 4 ] [ 5 ]  Odorant binding to the cilia of an ORN evokes an electrical response, kickstarting odor transduction. [ 4 ]  An individual ORN contains several  microvilli , olfactory cilia, which protrude from a knoblike structure at the  apical surface  involved in  dendritic processes . [ 4 ]  The olfactory cilia lack the  cytoskeletal  features of  motile cilia  and are, therefore, more similar to microvilli like that found in the lungs or gut. [ 4 ]  Olfactory cilia are  actin -rich protrusions supported by  scaffolding proteins  which help to localize odorant receptors and provide an increased cellular surface for odorant binding. [ 4 ]


Homologous  to  G-protein-coupled receptors (GPCRs) , olfactory receptor molecules consist of seven trans-membrane,  hydrophobic  domains and a cytoplasmic domain with a  carboxyl terminal  region that interacts with  G-proteins  and odorants. [ 4 ] [ 5 ]  Once an odorant is bound to an odor receptor protein, the alpha subunit of an olfactory-specific heterotrimeric G-protein, G olf , dissociates and activates olfactory-specific  adenylate cyclase , adenylyl cyclase III (ACIII). [ 4 ] [ 5 ]  Activation of ACIII leads to an increase in  cyclic AMP  (cAMP), which  depolarizes  the neuron due to an influx of Na+ and Ca2+ by opening  cyclic nucleotide-gated ion channels . [ 4 ] [ 5 ]  The neuron is further depolarized by a Ca2+-activated Cl- current travelling from the cilia, where the depolarization first occurred, to the  axon hillock  of the ORN. [ 4 ] [ 5 ]  At the axon hillock,  voltage-gated Na+ channels  open and generate an  action potential  that is transmitted to the  olfactory bulb . [ 4 ] [ 5 ]  After transmission, the ORN membrane is repolarized by  calcium/calmodulin kinase  II-mediated mechanisms that work to extrude Ca2+ and transport Na+ via an Na+/Ca2+ exchanger, diminish cAMP levels by activating  phosphodiesterases , and restore heterotrimeric G olf. [ 4 ]


ORN axons are responsible for relaying odorant information to CNS through action potentials. [ 4 ] [ 6 ]  The ORN axons leave the olfactory epithelium and travel  ipsilaterally  to the olfactory bulb where the ORN axons coalesce into multiple clusters, called  glomeruli , which together form the olfactory nerve. [ 4 ] [ 5 ] [ 6 ]  The ORN axons of each glomerulus synapse with apical dendrites of  mitral cells , the primary projection neurons of the olfactory bulb, which create and send action potentials further into the CNS. [ 4 ] [ 5 ] [ 6 ]


ORNs directly interact with odorants inhaled into the olfactory epithelium which can also subject the ORNs to damage through continuous exposure to harmful substances such as  airborne pollutants ,  microorganisms , and  allergens . [ 4 ] [ 6 ] [ 7 ]  Therefore, ORNs maintain a normal cycle of degeneration and regeneration. [ 4 ] [ 7 ]  The olfactory epithelium consists of three main cell types: supporting cells, mature ORNs, and basal cells. [ 4 ] [ 7 ]  Regeneration of ORNs requires the division of basal cells,  neural stem cells , to produce new receptor neurons. [ 4 ] [ 6 ] [ 7 ]  This regeneration process makes ORNs unique when compared to other neurons. [ 4 ]


In the nasal passages, inhaled odorant molecules interact with receptor proteins on localized neuronal cilia of ORNs. [ 5 ] [ 6 ]  These dendritic extensions, cilia, express one type of protein receptor, although individual odorants can interact with multiple different receptor proteins. [ 5 ] [ 6 ]  As new ORNs mature, they have decreased expression levels of multiple olfactory receptor  genes , contrasting with mature ORNs firm rule of one neuron—one expressed olfactory receptor gene. [ 4 ] [ 6 ]  Moreover, different odors activate specific ORNs in a molecular and spatial manner due to receptor specificity. [ 4 ]  Some ORNs contain receptor proteins with high affinity for some odorants, with distinct odor selectivity to a specific chemical structure, while other receptor proteins are less selective. [ 4 ]


Damage to this nerve leads to impairment or total loss of the sense of smell ( anosmia ). To simply test the function of the olfactory nerve, each  nostril  is tested with a pungent odor. If the odor is smelled, the olfactory nerve is likely functioning. On the other hand, the nerve is only one of several reasons that could explain if the odor is not smelled. There are olfactory testing packets in which strong odors are embedded into cards and the responses of the patient to each odor can be determined. [ 2 ]


Lesions to the olfactory nerve can occur because of "blunt trauma", such as  coup-contrecoup  damage, meningitis, and tumors of the  frontal lobe  of the brain. These injuries often lead to a reduced ability to taste and smell. Lesions of the olfactory nerve do not lead to a reduced ability to sense pain from the nasal epithelium. This is because pain from the nasal epithelium is not carried to the central nervous system by the olfactory nerve - it is carried to the central nervous system by the  trigeminal nerve .


A decrease in the ability to smell is a normal consequence of human  aging , and usually is more pronounced in men than in women. It is often unrecognized in patients except that they may note a decreased ability to taste (much of taste is actually based on reception of food odor). Some of this decrease results from repeated damage to the olfactory nerve receptors due likely to repeated upper respiratory infections. Patients with  Alzheimer's disease  almost always have an abnormal sense of smell when tested. [ 2 ]


Some  nanoparticles  entering the nose are transported to the brain via olfactory nerve. This can be useful for  nasal administration  of medications. [ 8 ]  It can be harmful when the particles are soot [ 9 ]  or magnetite [ 10 ]  in  air pollution . [ 11 ]


In  naegleriasis , "brain-eating" amoeba enter through the olfactory mucosa of the nasal tissues and follow the olfactory nerve fibers into the olfactory bulbs and then the brain.


The  ophthalmic artery  ( OA ) is an artery of the head. It is the first branch of the  internal carotid artery  distal to the  cavernous sinus . Branches of the ophthalmic artery supply all the structures in the  orbit  around the  eye , as well as some structures in the  nose ,  face , and  meninges . Occlusion of the ophthalmic artery or its branches can produce sight-threatening conditions.


The ophthalmic artery emerges from the  internal carotid artery . [ 1 ]  This is usually just after the internal carotid artery emerges from the  cavernous sinus . In some cases, the ophthalmic artery branches just before the internal carotid exits the cavernous sinus. The ophthalmic artery emerges along the medial side of the  anterior clinoid process . It runs anteriorly, passing through the  optic canal  inferolaterally to the  optic nerve . [ 1 ]  It can also pass superiorly to the optic nerve in a minority of cases. [ 2 ]  In the posterior third of the cone of the orbit, the ophthalmic artery turns sharply and medially to run along the medial wall of the orbit.


Because of the obvious importance of the ocular globe, branches of the ophthalmic artery often are subdivided into two groups: those that supply the eyeball (ocular group) and those that supply non-ocular orbital structures (orbital group). [ 3 ]


The orbital group, distributing vessels to the orbit and surrounding parts, includes:


The ocular group, distributing vessels to the eye and its muscles, includes:


The  central retinal artery  is the first, and one of the smaller branches of the ophthalmic artery and runs in the dura mater inferior to the optic nerve. About 12.5mm (0.5 inch) posterior to the globe, the central retinal artery turns superiorly and penetrates the  optic nerve , continuing along the center of the optic nerve, entering the eye to supply the inner retinal layers.


The next branch of the ophthalmic artery is the  lacrimal artery , one of the largest, arises just as the OA enters the orbit and runs along the superior edge of the  lateral rectus muscle  to supply the  lacrimal gland ,  eyelids  and  conjunctiva .


The ophthalmic artery then turns medially, giving off 1 to 5  posterior ciliary arteries  (PCA) that subsequently branch into the long and short posterior ciliary arteries (LPCA and SPCA respectively) which perforate the sclera posteriorly in the vicinity of the optic nerve and macula to supply the posterior uveal tract. In the past, anatomists made little distinction between the posterior ciliary arteries and the short and long posterior ciliary arteries often using the terms synonymously. However, recent work by Hayreh has shown that there is both an anatomic and clinically useful distinction. [ 4 ]   The PCAs arise directly from the OA and are end arteries which is to say no PCA or any of its branches anastomose with any other artery. Consequently, sudden occlusion of any PCA will produce an infarct in the region of the choroid supplied by that particular PCA. Occlusion of a short or long PCA will produce a smaller choroidal infarct, within the larger area supplied by the specific parent PCA.


The ophthalmic artery continues medially the superior and inferior muscular branches arise either from the ophthalmic artery directly or a single trunk from the ophthalmic artery subsequently divides into superior and inferior branches to supply the  extraocular muscles .


The  supraorbital artery  branches from the ophthalmic artery as it passes over the optic nerve. The supraorbital artery passes anteriorly along the medial border of the  superior rectus  and  levator palpebrae  and through the  supraorbital foramen  to supply muscles and skin of the forehead.


After reaching the medial wall of the orbit, the ophthalmic artery again turns anteriorly. The  posterior ethmoidal artery  enters the nose via the posterior ethmoidal canal and supplies the posterior ethmoidal sinuses and enters the skull to supply the meninges.


The OA continues anteriorly, giving off the  anterior ethmoidal artery  which enters the nose after traversing the anterior ethmoidal canal and supplies the anterior and middle ethmoidal sinuses, as well as the frontal sinus and also enters the cranium to supply the meninges.


The OA continues anteriorly to the trochlea, where the medial palpebral arteries (superior and inferior) arise and supply the eyelids.


The OA terminates in two branches, the supratrochlear (or frontal) artery and the dorsal nasal artery. Both exit the orbit medially to supply the forehead and scalp.


Branches of the ophthalmic artery supply:


Severe occlusion of the ophthalmic artery causes  ocular ischemic syndrome . As with  central retinal artery  occlusions, ophthalmic artery occlusions may result from systemic  cardiovascular diseases ; however, a  cherry-red spot  is typically absent and the vision is usually worse.  Amaurosis fugax  is a temporary loss of vision that occurs in two conditions which cause a temporary reduction in ophthalmic artery pressure:  orthostatic hypotension  and positive acceleration. [ 5 ]


Even complete occlusion of the ophthalmic artery may possibly leave the eye without symptoms, probably because of  circulatory anastomoses [ 6 ]


The  ophthalmic nerve  ( CN V 1 ) is a sensory nerve of the head. It is one of three divisions of the  trigeminal nerve (CN V) , a  cranial nerve . It has three major branches which provide sensory innervation to the  eye , and the  skin  of the upper face and anterior  scalp , as well as other structures of the head.


It measures about 2.5 cm in length. [ citation needed ]


The ophthalmic nerve is the first branch of the  trigeminal nerve (CN V) , the first and smallest of its three divisions. [ 1 ]  It arises from the superior part of the  trigeminal ganglion . [ citation needed ]


It passes anterior-ward along the lateral wall of the  cavernous sinus  inferior to the  oculomotor nerve (CN III)  and  trochlear nerve (N IV) . [ 1 ]  It exits the skull into the orbit through the  superior orbital fissure . [ 2 ]


Within the skull, the ophthalmic nerve produces: [ 1 ]


The ophthalmic nerve divides into three major branches which pass through the superior orbital fissure: [ 1 ]


The ophthalmic nerve provides sensory innervation to the  cornea ,  ciliary body , and  iris ; to the  lacrimal gland  and  conjunctiva ; to the part of the  mucous membrane  of the  nasal cavity ; and to the skin of the  eyelids ,  eyebrow ,  forehead  and  nose .


It carries sensory branches from the eyes, conjunctiva, lacrimal gland, nasal cavity, frontal sinus, ethmoidal cells, falx cerebri, dura mater in the anterior cranial fossa, superior parts of the tentorium cerebelli, upper eyelid, dorsum of the nose, and anterior part of the scalp.


Roughly speaking, the ophthalmic nerve supplies general somatic afferents to the upper face, head, and eye:


In comparison, the  maxillary nerve (CN V2)  provides general somatic afferents to the mid-face and mid-head.


Damage to the ophthalmic nerve can cause loss of sensation of the structures it supplies in the face. [ 3 ]  The  corneal reflex  may be lost, which can increase the risk of damage to the  cornea . [ 3 ]


This article incorporates text in the  public domain  from  page 887  of the 20th edition of   Gray's Anatomy   (1918)


In  neuroanatomy , the  optic nerve , also known as the  second cranial nerve ,  cranial nerve II , or simply  CN II , is a paired  cranial nerve  that transmits  visual  information from the  retina  to the  brain . In humans, the optic nerve is derived from  optic stalks  during the seventh week of development and is composed of  retinal ganglion cell  axons and  glial cells ; it extends from the  optic disc  to the  optic chiasma  and continues as the  optic tract  to the  lateral geniculate nucleus ,  pretectal nuclei , and  superior colliculus . [ 1 ] [ 2 ]


The optic nerve has been classified as the second of twelve paired  cranial nerves , but it is technically a myelinated tract of the  central nervous system , rather than a classical nerve of the  peripheral nervous system  because it is derived from an out-pouching of the  diencephalon  ( optic stalks ) during embryonic development. As a consequence, the fibers of the optic nerve are covered with  myelin  produced by  oligodendrocytes , rather than  Schwann cells  of the peripheral nervous system, and are encased within the  meninges . [ 3 ]   Peripheral neuropathies  like  Guillain–Barré syndrome  do not affect the optic nerve. However, most typically, the optic nerve is grouped with the other eleven cranial nerves and is considered to be part of the peripheral nervous system.


The optic nerve is ensheathed in all three meningeal layers ( dura ,  arachnoid , and  pia mater ) rather than the  epineurium ,  perineurium , and  endoneurium  found in peripheral nerves.  Fiber tracts  of the mammalian central nervous system have only limited regenerative capabilities compared to the peripheral nervous system. [ 4 ]  Therefore, in most mammals, optic  nerve damage  results in irreversible  blindness . The fibers from the  retina  run along the optic nerve to nine primary visual nuclei in the brain, from which a major relay inputs into the  primary visual cortex .


The optic nerve is composed of  retinal ganglion cell  axons and  glia . Each human optic nerve contains between 770,000 and 1.7 million nerve fibers, [ 5 ]  which are axons of the retinal ganglion cells of one retina. In the  fovea , which has high acuity, these ganglion cells connect to as few as 5  photoreceptor cells ; in other areas of the retina, they connect to thousands of photoreceptors.


The optic nerve leaves the  orbit  (eye socket) via the  optic canal , running postero-medially towards the  optic chiasm , where there is a partial decussation (crossing) of fibers from the temporal  visual fields  (the nasal hemi-retina) of both eyes. The proportion of decussating fibers varies between species, and is correlated with the degree of  binocular vision  enjoyed by a species. [ 6 ]  Most of the  axons  of the optic nerve terminate in the  lateral geniculate nucleus  from where information is relayed to the  visual cortex , while other axons terminate in the  pretectal area [ 7 ]  and are involved in reflexive  eye movements . Other axons terminate in the  suprachiasmatic nucleus  and are involved in regulating the  sleep-wake cycle . Its diameter increases from about 1.6 mm within the eye to 3.5 mm in the orbit to 4.5 mm within the cranial space. The optic nerve component lengths are 1 mm in the globe, 24 mm in the orbit, 9 mm in the optic canal, and 16 mm in the cranial space before joining the optic chiasm. There, partial decussation occurs, and about 53% of the fibers cross to form the optic tracts. Most of these fibers terminate in the lateral geniculate body. [ 1 ]


Based on this anatomy, the optic nerve may be divided into four parts as indicated in the image at the top of this section (this view is from above as if you were looking into the orbit after the top of the skull had been removed): 1. the optic head (which is where it begins in the eyeball (globe) with fibers from the retina); 2. orbital part (which is the part within the orbit); 3. intracanicular part (which is the part within a bony canal known as the optic canal); and, 4. cranial part (the part within the cranial cavity, which ends at the optic chiasm). [ 2 ]


From the lateral geniculate body, fibers of the  optic radiation  pass to the  visual cortex  in the  occipital lobe  of the brain. In more specific terms, fibers carrying information from the contralateral superior visual field traverse Meyer's loop to terminate in the  lingual gyrus  below the  calcarine fissure  in the occipital lobe, and fibers carrying information from the contralateral inferior visual field terminate more superiorly, to the  cuneus . [ 8 ]


The optic nerve transmits all visual information including  brightness  perception,  color perception  and  contrast  ( visual acuity ). It also conducts the visual impulses that are responsible for two important neurological reflexes: the  light reflex  and the  accommodation reflex . The light reflex refers to the constriction of both  pupils  that occurs when light is shone into either eye. The accommodation reflex refers to the swelling of the  lens of the eye  that occurs when one looks at a near object (for example: when reading, the lens adjusts to near vision). [ 1 ]


The eye's  blind spot  is a result of the absence of photoreceptors in the area of the retina where the optic nerve leaves the eye. [ 1 ]


Damage to the optic nerve typically causes permanent and potentially severe loss of  vision , as well as an abnormal pupillary reflex, which is important for the diagnosis of nerve damage.


The type of  visual field  loss will depend on which portions of the optic nerve were damaged. In general, the location of the damage in relation to the optic chiasm (see diagram above) will affect the areas of vision loss. Damage to the optic nerve that is  anterior , or in front of the optic chiasm (toward the face) causes loss of vision in the eye on the same side as the damage. Damage at the optic chiasm itself typically causes loss of vision laterally in both visual fields or  bitemporal hemianopsia  (see image to the right). Such damage may occur with large  pituitary  tumors, such as  pituitary adenoma . Finally, damage to the  optic tract , which is posterior to, or behind the chiasm, causes loss of the entire visual field from the side opposite the damage, e.g. if the left optic tract were cut, there would be a loss of vision from the entire right visual field.


Injury to the optic nerve can be the result of  congenital  or inheritable problems like  Leber's hereditary optic neuropathy ,  glaucoma , trauma,  toxicity ,  inflammation ,  ischemia ,  infection  (very rarely), or compression from  tumors  or  aneurysms . By far, the three most common injuries to the optic nerve are from glaucoma;  optic neuritis , especially in those younger than 50 years of age; and anterior  ischemic optic neuropathy , usually in those older than 50.


Glaucoma  is a group of diseases involving loss of retinal ganglion cells causing  optic neuropathy  in a pattern of  peripheral vision  loss, initially sparing central vision.  Glaucoma is frequently associated with increased intraocular pressure that damages the optic nerve as it exits the eyeball. The  trabecular meshwork  assists the drainage of  aqueous humor  fluid. The presence of excess aqueous humor, increases IOP, yielding the diagnosis and symptoms of glaucoma. [ 9 ]


Optic neuritis  is inflammation of the optic nerve. It is associated with a number of diseases, the most notable one being  multiple sclerosis .  The patient will likely experience varying vision loss and eye pain.  The condition tends to be episodic.


Anterior ischemic optic neuropathy  is commonly known as a "stroke of the optic nerve" and affects the optic nerve head (where the nerve exits the eyeball). There is usually a sudden loss of blood supply and nutrients to the optic nerve head. Vision loss is typically sudden and most commonly occurs upon waking up in the morning. This condition is most common in diabetic patients 40–70 years old.


Other optic nerve problems are less common.  Optic nerve hypoplasia  is the underdevelopment of the optic nerve resulting in little to no vision in the affected eye. Tumors, especially those of the pituitary gland, can put pressure on the optic nerve causing various forms of visual loss. Similarly,  cerebral aneurysms , a swelling of  blood vessel(s) , can also affect the nerve. Trauma can cause serious injury to the nerve. Direct optic nerve injury can occur from a penetrating injury to the orbit, but the nerve can also be injured by indirect trauma in which severe head impact or movement stretches or even tears the nerve. [ 1 ]


Ophthalmologists  and  optometrists  can detect and diagnose some optic nerve diseases but  neuro-ophthalmologists  are often best suited to diagnose and treat diseases of the optic nerve. The International Foundation for Optic Nerve Diseases (IFOND) sponsors research and provides information on a variety of optic nerve disorders.


Oral allergy syndrome  ( OAS ) or  pollen-food allergy syndrome  ( PFAS ) is a type of  allergy  classified by a cluster of allergic reactions in the mouth and throat in response to eating certain (usually fresh)  fruits ,  nuts , and  vegetables . It typically develops in adults with  hay fever . [ 1 ]  It is not usually serious. [ 2 ]


OAS is the result of  cross-reactivity  between  antigens  of tree or weed pollen and antigens found in certain fruits and vegetables.  Therefore, OAS is only seen in people with seasonal pollen allergies, and mostly people who are allergic to tree  pollen . [ 3 ]   It is usually limited to ingestion of uncooked fruits or vegetables. [ 3 ]
In adults, up to 60% of all food allergic reactions are due to cross-reactions between foods and inhalative allergens. [ 4 ]


OAS is a class II allergy where the body's immune system produces IgE  antibodies  against pollen; in OAS, these antibodies also bind to (or cross-react with) other structurally similar proteins found in botanically related plants. This differs from class 1  food allergy  where sensitisation to the protein occurs in the GI tract, and is produced as a result of exposure to the food itself. [ 5 ]


OAS can occur any time of the year, but is most prevalent during the pollen season. Individuals with OAS usually develop symptoms within minutes of eating the food. [ 6 ]


Individuals with OAS may have any of a number of allergic reactions that usually occur very rapidly, within minutes of eating a trigger food.  The most common reaction is an itching or burning sensation in the lips, mouth, ear canal, or  pharynx . Sometimes other reactions can be triggered in the eyes, nose, and skin.  Swelling of the lips, tongue, and  uvula , and a sensation of tightness in the throat may be observed. Once the allergen reaches the
stomach, it is broken down by the acid, and the allergic reaction does not progress further. [ 7 ] : 405   The natural course of the disease is that it usually persists. [ 7 ] : 407


If an affected person swallows the raw food, and the allergen is not destroyed by the stomach acids, it is likely that there will be a reaction from histamine release later in the  gastrointestinal tract .  Vomiting ,  diarrhea , severe  indigestion , or  cramps  may occur. [ 6 ]  Rarely, OAS may be severe and present as wheezing, vomiting, hives,  low blood pressure , [ 8 ]  or  anaphylaxis . [ 9 ]


A person with an allergic disposition is sensitized to allergenic pollen proteins through the respiratory route can develop an allergy to heat labile food proteins (for example  profilins ) in certain fruits and vegetables, which cross-react with pollen proteins. [ 7 ] : 409


OAS produces symptoms when an affected person eats certain fruits, vegetables, and nuts. Some individuals may only show allergy to one particular food, and others may show an allergic response to many foods. [ 1 ] [ dead link  ]


Individuals with an allergy to tree pollen may develop OAS to a variety of foods. While the tree pollen allergy has been worked out, the grass pollen is not well understood. Furthermore, some individuals have severe reactions to certain fruits and vegetables that do not fall into any particular allergy category. When tropical foods initiate OAS, allergy to  latex  may be the underlying cause. [ 10 ]


Because the allergenic proteins associated with OAS are usually destroyed by cooking, most reactions are caused by eating raw foods. [ 7 ]  The main exceptions to this are celery and nuts, which may cause reactions even after being cooked. [ 11 ]


Allergies to a specific pollen are usually associated with OAS reactions to other certain foods.  For instance, an allergy to  ragweed  is associated with OAS reactions to  banana ,  watermelon ,  cantaloupe ,  honeydew ,  zucchini ,  kiwifruit , and  cucumber . This does not mean that everyone with an allergy to ragweed will experience adverse effects from all or even any of these foods. Reactions may be associated with one type of food, with new reactions to other foods developing later. However, reaction to one or more foods in any given category does not necessarily mean a person is allergic to all foods in that group. [ citation needed ]