Each anesthesia technique has its advantages and disadvantages, and the selection of anesthesia will depend on various factors including the surgeon's and patient's choice, disease and additional surgical steps required. [ citation needed ]


Vitrectomy was originated by  Robert Machemer [ 3 ]  with contributions from Thomas M. Aaberg Sr in late 1969 and early 1970. The original purpose of vitrectomy was to remove clouded vitreous humor—usually containing blood. [ citation needed ]


The success of these first procedures led to the development of techniques and instruments to remove clouding and also to peel scar tissue off the light sensitive lining of the eye—the  retina — membranectomy , to provide space for materials injected in the eye to reattach the retina such as gases or liquid silicone, and to increase the efficacy of other surgical steps such as  scleral buckle .


The development of new instruments and surgical strategies through the 1970s and 1980s was spearheaded by surgeon and engineer  Steve Charles . [ 4 ]  More recent advances have included smaller and more refined instruments for use in the eye, the injection of various medications at the time of surgery to manipulate a detached retina into its proper position and mark the location of tissue layers to allow their removal, and for long term protection against scar tissue formation. Several technologies and systems exist to treat vitrectomy. [ 5 ]


Additional surgical steps involved as part of modern vitrectomy surgeries may include:


Membranectomy  – removal of layers of unhealthy tissue from the retina with minute instruments such as forceps (tiny grasping tools), picks (miniature hooks), and visco-dissection (separating layers of tissue with jets of fluid.) This layer of unhealthy tissue is called an epiretinal membrane and it can occur in anyone, but is more likely to occur in the elderly or in people who have had prior eye disease or eye surgery. [ 6 ]  If the patient has an epiretinal membrane and is also complaining of symptoms such as decreased visual acuity, then a membranectomy is performed in addition to the vitrectomy. Complications of this additional step are similar to complications of the standard vitrectomy procedure. [ 6 ]


Fluid/air exchange  – injection of air into the eye to remove the intraocular fluid from the posterior segment of the globe while maintaining intraocular pressure to temporarily hold the retina in place or seal off holes in the retina. The air pressure is temporary as the posterior segment will soon re-fill with fluid.


Air/gas exchange  – In some cases, gas can be used to help hold the retina in place. Gas, or more typically mixed gas and air, is injected through the sclera and into the posterior segment of the globe. This procedure is often referred to as pneumatic retinopexy. Typical gases used are  perfluoropropane  or  sulfur hexafluoride . The gases are mixed with air to neutralize their expansive properties to provide for a longer acting (than air alone) retinal  tamponade . The retinal tamponade acts to hold the retina in place or temporarily seal off holes in the retina. The mixed gases disappear spontaneously once they have accomplished their purpose and the posterior segment re-fills with fluid. [ 7 ]


Silicone oil injection  – Similar to an air/gas exchange, or pneumatic retinopexy, the eye can also be filled with  liquid silicone  to hold the retina in place. [ 7 ]  In contrast to the pneumatic retinopexy, however, the silicone oil remains in the eye until it is later removed surgically. Oils have less surface tension and buoyancy than gases so the tension exerted by the oil is about 30 times less than that of the gas. [ 8 ]


Photocoagulation  – In cases when there is a tear in the retina, or when there are unhealthy damaging blood vessels (which can be seen in patients with diabetic retinopathy), laser treatment can be used. [ 7 ]  In such cases, the laser is used to seal the hole or prevent growth of the unhealthy, damaging blood vessels.


Scleral buckling  – placement of a support positioned like a belt around the eyeball to maintain the retina in a proper, attached position. This is referred to as an "exoplant". Placement of the scleral buckle for patients who have had a retinal detachment has been shown to lead to reattachment approximately 80 to 90 percent of the time after one surgery. In cases of failure, most patients are treated with vitrectomy.


Lensectomy  – In some cases, a lensectomy, or "cataract surgery", is done in conjunction with the vitrectomy. This extra procedure is performed when the lens of eye is cloudy (cataract), damaged during the vitrectomy, if there is attached to scar tissue, or if the pressure in the eye needs to be lowered (as in the case with some glaucomatous patients). [ 7 ]


Conditions which can benefit from vitrectomy include:


Retinal detachment  – a blinding condition where the lining of the eye peels loose and floats freely within the interior of the eye. Steps to reattach the retina  may include vitrectomy to clear the inner jelly, scleral buckling to create a support for the reattached retina, membranectomy to remove scar tissue, injection of dense liquids to smooth the retina into place, photocoagulation to bond the retina back against the wall of the eye, and injection of a gas or silicone oil to secure the retina in place as it heals.


Macular pucker  – formation of a patch of unhealthy tissue in the central retina (the  macula ) distorting vision. Also called  epiretinal membrane . After vitrectomy to remove the vitreous gel, membranectomy is undertaken to peel away the tissue.


Diabetic retinopathy  – may damage sight by either a non-proliferative or proliferative retinopathy. The proliferative type is characterized by formation of new unhealthy, freely bleeding blood vessels within the eye (called vitreal hemorrhage) and/or causing thick fibrous scar tissue to grow on the retina, detaching it. Often diabetic retinopathy is treated in early stages with a laser in the physician's office to prevent these problems. When bleeding or retinal detachment occur, vitrectomy is employed to clear the blood, membranectomy removes scar tissue, and injection of gas or silicone with scleral buckle may be needed to return sight. Diabetics should have an eye exam yearly.


Macular holes  – the normal shrinking of the vitreous humor with aging can occasionally tear the central retina causing a macular hole with a blind spot blocking sight.


Vitreous hemorrhage  – bleeding in the eye from injuries, retinal tears,  subarachnoid hemorrhages  (as  Terson syndrome ), or blocked blood vessels. Once blood is removed,  photocoagulation  with a laser can shrink unhealthy blood vessels or seal retinal holes.


Vitreous floaters  – deposits of various size, shape, consistency, refractive index, and motility within the eye's normally transparent vitreous humor which can obstruct vision. Here pars plana vitrectomy has been shown to relieve symptoms. [ 9 ]  Because of possible side effects it is used only in severe cases.


There are a few complications that can result from vitrectomy surgery.  Cataract  is the most frequent complication. Many patients will develop a cataract within the first few years after surgery. [ 10 ]  Because there have been no published controlled trials evaluating the benefits and risks stemming from post vitrectomy cataract surgery, ophthalmologists have no clear evidence to rely upon when counseling patients about cataract surgery. [ 11 ]


Other common complications include high intraocular pressure, bleeding in the eye, and  retinal edema , swelling in the back of the eye. [ 12 ]  In most cases, the retinal edema can be managed with over-the-counter medication. In severe cases, this swelling can be treated with intra-ocular injections. [ 13 ]


More severe complications after a vitrectomy are  endophthalmitis  (inflammation of the fluids in the eye) or suprachoroidal hemorrhage (bleeding above the choroidal layer of the eye). Rates of these complications have been reported to be less than 0.5%.


Lastly, although vitrectomy surgery is often done to correct retinal detachments, a subsequent retinal detachment is a possible complication as well. Rates of retinal detachment have been reported to be less than 5%.


Patients use eye drops for several weeks, or longer, to allow the surface of the eye to heal. In some cases, heavy lifting is avoided for a few weeks.


A gas bubble may be placed inside the eye, to keep the retina in place. If a gas bubble is used, sometimes a certain head positioning ( posturing ) has to be maintained, such as face down or sleeping on the right or left side.  The gas bubble will dissolve over time, but this takes several weeks.  Flying should be avoided while the gas bubble is still present.


Problems such as return of the original condition, bleeding, or infection from the surgery may require additional treatment or can result in blindness.  In the event that the patient would need to remain face down after surgery, a vitrectomy support system can be rented, to help aid during the recovery time.  This particular equipment may be used for as little as five days to as long as three weeks. A  Cochrane review  found that in one study, cataract surgery was needed within two years for about half of the eyes operated on for idiopathic macular hole, and retinal detachment was found in about one in 20 eyes. [ 14 ]


The return of eyesight after vitrectomy depends on the underlying condition which prompted the need for surgery. It also depends on patient age and their visual acuity before surgery. For example, if the eye is healthy, but filled with blood, then vitrectomy can result in return of  20/20  eyesight. With more serious problems, such as a retina which has detached several times, final sight may be only sufficient to safely walk ( ambulatory vision ) or less.


With a  retinal detachment , some very important considerations are how long the retina has been detached, and what part of the retina was detached. For example, if the  macula  of the retina comes off too, outcomes might not be as good as they would if the macula was still attached. Also, the longer the time between the detachment and the reattachment, the worse the outcomes. Some ophthalmologists believe that if a patient has a retinal detachment that involves the macula and it has been longer than 6 months, then a vitrectomy for that patient is unlikely to help. However, recent studies have shown that visual improvement might still be found in these patients. Given the high variability between outcomes for different patients with retinal detachments, it is very important to be examined by an ophthalmologist as soon as possible.


A Cochrane review found vitrectomy for patients with idiopatic macular hole improved visual acuity by about 1.5 lines on an acuity chart. Macular hole closure was 76% in those treated with vitrectomy compared to 11% in those observed. [ 14 ]


In 1996,  Spalding Gray , an American actor, screenwriter and playwright, released  Gray's Anatomy , a film monologue describing his experiences dealing with a  macular pucker  and his decision to undergo surgery. [ 15 ]


Vitreomacular adhesion  ( VMA ) is a  human   medical condition  where the  vitreous gel  (or simply vitreous, AKA vitreous humour) of the  human eye  adheres to the  retina  in an abnormally strong manner. As the eye ages, it is common for the vitreous to separate from the retina. But if this separation is not complete, i.e. there is still an  adhesion , this can create pulling forces on the retina that may result in subsequent loss or distortion of vision. The adhesion in of itself is not dangerous, but the resulting pathological  vitreomacular traction  (VMT) can cause severe ocular damage.


The current  standard of care  for treating these adhesions is  pars plana vitrectomy  (PPV), which involves surgically removing the vitreous from the eye. A biological agent for non-invasive treatment of adhesions called  ocriplasmin  has been approved by the FDA on October 17, 2012.


Traction caused by VMA is the underlying pathology of an eye disease called symptomatic VMA. There is evidence that symptomatic VMA can contribute to the development of several well-known eye disorders, such as macular hole and macular pucker, that can cause visual impairment, including blindness. It may also be associated with  age-related macular degeneration  (AMD),  diabetic macular edema  (DME),  retinal vein occlusion , and  diabetic retinopathy  (DR). [ citation needed ]


Over time, it is common for the vitreous within the human eye to  liquify  and collapse in processes known as  syneresis  and  synchisis  respectively. This creates fluid-filled areas that can combine to form pockets of vitreous gel that are mostly liquid with very small concentrations of  collagen . If these liquid pockets are close enough to the interface between the vitreous gel and the retina, they can cause complete separation of the vitreous from the retina in a normally occurring process in older humans called  posterior vitreous detachment  (PVD). PVD in of itself is not dangerous and a natural process. [ citation needed ]


If the separation of the vitreous from the retina is not complete, areas of focal attachment or adhesions can occur, i.e. a VMA. The pulling forces or traction from this adhesion on the retinal surface can sometimes cause  edema  within the retina, damage to retinal blood vessels causing  bleeding , or damage to the  optic nerve  causing disruption in the  nerve signals  sent to the  brain  for  visual processing . It is important to note that while the VMA itself is not dangerous, the resultant pulling on the retina called vitreomacular traction (VMT) causes the above damage. The size and strength of the VMA determine the variety of resulting  pathologies  or symptoms. [ 1 ]


VMA can also lead to the development of VMT/traction-related complications such as  macular puckers  and  macular holes  leading to  distorted vision  or  metamorphopsia ;  epiretinal membrane ;  tractional macular oedema ;  myopic macular retinoschisis ; visual impairment; blindness. The incidence of VMA is reported as high as 84% for patients with  macular hole , 100% for patients with  vitreomacular traction syndrome , and 56% in  idiopathic epimacular membrane . [ 2 ]


Careful eye examination by an  ophthalmologist  or  optometrist  is critical for diagnosing symptomatic VMA. Imaging technologies such as  optical coherence tomography  (OCT) have significantly improved the accuracy of diagnosing symptomatic VMA. [ citation needed ]


A new FDA approved drug was released on the market late 2013.  Jetrea (Brand name) or Ocriplasmin  (Generic name) is the first drug of its kind used to treat vitreomacular adhesion. [ citation needed ]


Mechanism of Action: Ocriplasmin is a truncated human plasmin with proteolytic activity against protein components of the vitreous body and vitreoretinal interface. It dissolves the protein matrix responsible for the vitreomacular adhesion.
Adverse drug reactions: Decreased vision, potential for lens subluxation, dyschromatopsia (yellow vision), eye pain, floaters, blurred vision.
New Drug comparison Rating gave Jetea a 5 indicating an important advance.
Previously, no recommended treatment was available for the patient with mild symptomatic VMA. In symptomatic VMA patients with more significant vision loss, the standard of care is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye, thereby surgically releasing the symptomatic VMA. In other words, vitrectomy induces PVD to release the traction/adhesion on the retina. An estimated 850,000 vitrectomy procedures are performed globally on an annual basis with 250,000 in the United States alone.


A standard PPV procedure can lead to serious complications [ 3 ] [ 4 ] [ 5 ] [ 6 ]  including small-gauge PPV. [ 7 ] [ 8 ] [ 9 ] [ 10 ] [ 11 ]  Complications can include  retinal detachment ,  retinal tears ,  endophthalmitis , and postoperative  cataract  formation. Additionally, PPV may result in incomplete separation, and it may potentially leave a  nidus  for  vasoactive  and  vasoproliferative  substances, or it may induce development of  fibrovascular membranes . As with any invasive surgical procedure, PPV introduces  trauma  to the vitreous and surrounding tissue. [ 12 ] [ 13 ]


There are data showing that nonsurgical induction of PVD using  ocriplasmin  (a  recombinant   protease  with activity against  fibronectin  and  laminin ) [ 14 ]  can offer the benefits of successful PVD while eliminating the risks associated with a surgical procedure, i.e. vitrectomy.  Pharmacologic  vitreolysis is an improvement over invasive surgery as it induces complete separation, creates a more physiologic state of the vitreomacular interface, prevents the development of fibrovascular membranes, is less traumatic to the vitreous, and is potentially  prophylactic . [ 15 ] [ 16 ]  As of 2012,  ThromboGenics  is still developing the ocriplasmin biological agent. Ocriplasmin is approved recently under the name Jetrea for use in the  United States  by the  FDA .view. [ 17 ]


An experimental test of injections of  perfluoropropane  (C 3 F 8 ) on 15 symptomatic eyes of 14 patients showed that vitreomacular traction resolved in 6 eyes within 1 month and resolved in 3 more eyes within 6 months. [ 18 ]  A systematic review found high-certainty evidence that Ocriplasmin compared to no treatment increases the chance of resolution and improves vision in people with symptomatic VMA.  [ 19 ]  Ocriplasmin probably reduces the need for surgery but there were more adverse events in eyes treated with ocriplasmin compared to control.


The  von Graefe  knife  was a tool used to make corneal incisions in  cataract surgery . [ 1 ]  Use of the knife demanded a high level of skill and mastery, and was eventually supplanted by modifications of cataract surgery through the Kelman  phacoemulsification  technique that emphasized a small incision. [ 2 ]


Until the acceptability of the keratome-and-scissors method after the early 1940s, an essential part of  cataract  surgery was mastery of the von Graefe knife. With increased popularity of  sutures —especially pre-placed scleral groove (McLean) sutures, it became difficult for the occasional surgeon to develop the skill required to make an acceptable von Graefe incision. If the surgeon was not ambidextrous, the use of the von Graefe knife might be even more difficult with the non-dominant hand. With his right hand, he introduced the knife into the anterior chamber of the right eye at 9. He would then perforate the  limbal  area at 3. An upward sweep was then made to complete the incision. Most frequently, there was no conjunctival flap. However, some especially skilled eye surgeons formed a conjunctival flap as they were completing the upward sweep. Normally, the ambidextrous von Graefe surgeon would switch to his left hand so that he could enter the left eye at 3 and exit at 9. If he used his dominant right hand for the left eye, the nose became an impediment when he attempted to enter the eye at 9 and attempted to counter perforate at 3. Often, poor results could have been prevented by the use of post-placed sutures. Unfortunately, in the early years of cataract surgery, suitable sutures and needles were not in the  armamentarium  of many cataract surgeons.


In the 1980s, with the ever-increasing popularity of the Kelman  phacoemulsification  technique that emphasized a small incision and extra-capsular cataract extraction (ECCE), the keratome-and-scissors, large incision surgery technique combined with intracapsular cataract extraction (ICCE) became obsolete, although the use of the von Graefe knife still continued in India. Sutures had limited if any use in routine cataract surgery for the high-volume most experienced and skilled eye surgeons in the world. Their experience and skill resulted in the outstanding rural cataract camps so common in India. Formally trained Indian  ophthalmologists  were and are among the deftest in the use of the von Graefe knife.  Ultraviolet-rich India with its vast rural and underclass population afflicted with nutritional eye diseases combined with a multitude of public health problems was and still is the “Land of Eye Disease and Eye Surgery“. Few Western ophthalmologists have the daily volume of eye pathology and eye surgery that faces their Indian counterparts.


It is possible for an eye to recover from an intracapsular cataract operation that entailed a 170 to 180 degree superior corneal or limbal incision without the closure of the incisional wound by means of sutures. Recovery was significantly dependent on the quality of a well-made von Graefe knife incision with a well-honed and well-maintained knife. Unlike keratome-and-scissors incision, a well-performed von Graefe knife maneuver produced a corneal or limbal incision with well-opposed edges that resulted in rapid healing and a scar that was almost invisible to the naked eye. However, a poorly made von Graefe knife incision could lead to horrendous disasters.


or


Neurosurgery  or  neurological surgery , known in  common parlance  as  brain surgery , is the  medical specialty  that focuses on the surgical treatment or rehabilitation of disorders which affect any portion of the  nervous system  including the  brain ,  spinal cord ,  peripheral nervous system , and cerebrovascular system. [ 1 ]  Neurosurgery as a medical specialty also includes non-surgical management of some neurological conditions. [ 2 ]


In different countries, there are different requirements for an individual to legally practice neurosurgery, and there are varying methods through which they must be educated. In most countries, neurosurgeon training requires a minimum period of seven years after graduating from medical school. [ 3 ]


In the  United Kingdom , students must gain entry into medical school. The MBBS qualification ( Bachelor of Medicine, Bachelor of Surgery ) takes four to six years depending on the student's route. The newly qualified  physician  must then complete foundation training lasting two years; this is a paid training program in a hospital or clinical setting covering a range of medical specialties including surgery. Junior doctors then apply to enter the neurosurgical pathway. Unlike most other surgical specialties, it currently has its own independent training pathway which takes around eight years (ST1-8); before being able to sit for  consultant  exams with sufficient amounts of experience and practice behind them. Neurosurgery remains consistently amongst the most competitive medical specialties in which to obtain entry.


In the  United States , a neurosurgeon must generally complete four years of  undergraduate education , four years of  medical school , and seven years of  residency  (PGY-1-7). [ 4 ]  Most, but not all, residency programs have some component of basic science or clinical research. Neurosurgeons may pursue additional training in the form of a  fellowship  after residency, or, in some cases, as a senior resident in the form of an enfolded fellowship. These fellowships include  pediatric neurosurgery , trauma/neurocritical care, functional and  stereotactic  surgery, surgical neuro- oncology ,  radiosurgery , neurovascular surgery, skull-base surgery, peripheral nerve and complex spinal surgery. [ 5 ]  Fellowships typically span one to two years. In the U.S., neurosurgery is a very small, highly competitive specialty, constituting only 0.5 percent of all physicians. [ 6 ]


Neurosurgery, or the premeditated incision into the head for pain relief, has been around for thousands of years, but notable advancements in neurosurgery have only come within the last hundred years. [ 7 ]


The  Incas  appear to have practiced a procedure known as  trepanation  since before European colonization. [ 8 ]  During the  Middle Ages  in  Al-Andalus  from 936 to 1013 AD,  Al-Zahrawi  performed surgical treatments of head injuries, skull fractures, spinal injuries,  hydrocephalus , subdural effusions and headache. [ 9 ]  During the  Roman Empire , doctors and surgeons performed  neurosurgery  on depressed skull fractures. [ 10 ] [ 11 ]  Simple forms of neurosurgery were performed on  King Henri II  in 1559, after a  jousting  accident with  Gabriel Montgomery  fatally wounded him.  Ambroise Paré  and  Andreas Vesalius , both experts in their field at the time,
attempted their own methods, to no avail, in curing Henri. [ 12 ]  In China, Hua Tuo created the first general  anaesthesia  called mafeisan, which he used on surgical procedures on the brain. [ 13 ]


History of tumor removal : In 1879, after locating it via neurological signs alone, Scottish surgeon  William Macewen  (1848–1924) performed the first successful brain tumor removal. [ 4 ]   On November 25, 1884, after English physician  Alexander Hughes Bennett  (1848–1901) used Macewen's technique to locate it, English surgeon  Rickman Godlee  (1849–1925) performed the first primary brain tumor removal, [ 5 ] [ 14 ]  which differs from Macewen's operation in that Bennett operated on the exposed brain, whereas Macewen operated outside of the "brain proper" via  trepanation . [ 15 ]  On March 16, 1907, Austrian surgeon  Hermann Schloffer  became the first to successfully remove a  pituitary  tumor. [ 16 ]


Lobotomy : also known as  leucotomy , was a form of  psychosurgery , a neurosurgical treatment of  mental disorders  that involves severing connections in the brain's  prefrontal cortex . [ 17 ]  The originator of the procedure,  Portuguese  neurologist  António Egas Moniz , shared the  Nobel Prize for Physiology or Medicine  of 1949. [ 18 ] [ 19 ]  Some patients improved in some ways after the operation, but complications and impairments – sometimes severe – were frequent. The procedure was controversial from its initial use, in part due to the balance between benefits and risks. It is mostly rejected as a treatment now and non-compliant with  patients' rights .


History of electrodes in the brain : In 1878,  Richard Caton  discovered that electrical signals transmitted through an animal's brain.  In 1950 Jose Delgado invented the first electrode that was implanted in an animal's brain (bull), using it to make it run and change direction. [ 20 ]  In 1972 the  cochlear implant , a neurological  prosthetic  that allowed deaf people to hear was marketed for commercial use. In 1998 researcher Philip Kennedy implanted the first Brain Computer Interface (BCI) into a human subject. [ 21 ]


A survey done in 2010 on 100 most cited works in neurosurgery shows that the works mainly cover clinical trials evaluating surgical and medical therapies, descriptions of novel techniques in neurosurgery, and descriptions of systems classifying and grading diseases. [ 22 ]


The main advancements in neurosurgery came about as a result of highly crafted tools. Modern neurosurgical tools, or instruments, include  chisels , curettes, dissectors, distractors, elevators, forceps, hooks, impactors, probes, suction tubes, power tools, and robots. [ 23 ] [ 24 ]  Most of these modern tools have been in medical practice for a relatively long time. The main difference of these tools in neurosurgery, were the precision in which they were crafted. These tools are crafted with edges that are within a millimeter of desired accuracy. [ 25 ]  Other tools, such as hand held power saws and robots have only recently been commonly used inside of a neurological operating room. As an example, the University of Utah developed a device for computer-aided design / computer-aided manufacturing (CAD-CAM) which uses an image-guided system to define a cutting tool path for a robotic  cranial drill . [ 26 ]


The  World Federation of Neurosurgical Societies  ( WFNS ), founded in 1955, in  Switzerland , as a  professional ,  scientific ,  non governmental organization , is composed of 130 member societies: consisting of 5 Continental Associations ( AANS ,  AASNS ,  CAANS ,  EANS  and  FLANC ), 6 Affiliate Societies, and 119 National Neurosurgical Societies, representing some 50,000  neurosurgeons  worldwide. [ 27 ]  It has a consultative status in the  United Nations . The official Journal of the Organization is  World Neurosurgery . [ 28 ] [ 29 ]  The other global organisations being the World Academy of Neurological Surgery (WANS) and the World Federation of Skull Base Societies (WFSBS).


General neurosurgery involves most neurosurgical conditions including neuro-trauma and other neuro-emergencies such as  intracranial hemorrhage . Most level 1 hospitals have this kind of practice. [ 30 ]


Specialized branches have developed to cater to special and difficult conditions. These specialized branches co-exist with general neurosurgery in more sophisticated hospitals. To practice advanced specialization within neurosurgery, additional higher fellowship training of one to two years is expected from the neurosurgeon.
Some of these divisions of neurosurgery are:


According to an analysis by the  American College of Surgeons   National Surgical Quality Improvement Program  (NSQIP), the most common surgeries performed by neurosurgeons in between 2006 and 2014 were the following: [ 31 ]


Neuropathology  is a specialty within the study of  pathology  focused on the disease of the brain, spinal cord, and neural tissue. [ 32 ]  This includes the central nervous system and the peripheral nervous system. Tissue analysis comes from either surgical  biopsies  or post mortem  autopsies . Common tissue samples include muscle fibers and nervous tissue. [ 33 ]  Common applications of neuropathology include studying samples of tissue in patients who have  Parkinson's disease ,  Alzheimer's disease ,  dementia ,  Huntington's disease ,  amyotrophic lateral sclerosis ,  mitochondria disease , and any disorder that has neural deterioration in the brain or spinal cord. [ 34 ] [ 35 ]


While pathology has been studied for millennia only within the last few hundred years has medicine focused on a tissue- and organ-based approach to tissue disease. In 1810,  Thomas Hodgkin  started to look at the damaged tissue for the cause. This was conjoined with the emergence of microscopy and started the current understanding of how the tissue of the human body is studied. [ 36 ]


Neuroanesthesia is a field of  anesthesiology  which focuses on neurosurgery. Anesthesia is not used during the middle of an "awake" brain surgery. Awake brain surgery is where the patient is conscious for the middle of the procedure and sedated for the beginning and end. This procedure is used when the tumor does not have clear boundaries and the surgeon wants to know if they are invading on critical regions of the brain which involve functions like talking,  cognition , vision, and hearing. It will also be conducted for procedures which the surgeon is trying to combat  epileptic  seizures. [ 37 ]


The physician  Hippocrates  (460–370 BCE) made accounts of using different wines to  sedate  patients while trepanning. In 60 CE,  Dioscorides , a physician, pharmacologist, and botanist, detailed how  mandrake ,  henbane ,  opium , and alcohol were used to put patients to sleep during trepanning. In 972 CE, two brother surgeons in  Paramara , now India, used "samohine" to sedate a patient while removing a small tumor, and awoke the patient by pouring onion and vinegar in the patient's mouth. The combination of carbon dioxide, hydrogen, and nitrogen, was a form of neuroanesthesia adopted in the 18th century and introduced by  Humphry Davy . [ 38 ]


Various Imaging methods are used in modern neurosurgery diagnosis and treatment. They include  computer assisted imaging computed tomography (CT) ,  magnetic resonance imaging  (MRI),  positron emission tomography  (PET),  magnetoencephalography  (MEG), and  stereotactic radiosurgery . Some neurosurgery procedures involve the use of intra-operative MRI and functional MRI. [ 39 ]


In  conventional neurosurgery  the neurosurgeon opens the skull, creating a large opening to access the brain. Techniques involving smaller openings with the aid of microscopes and endoscopes are now being used as well. Methods that utilize small  craniotomies  in conjunction with high-clarity microscopic visualization of neural tissue offer excellent results. However, the open methods are still traditionally used in trauma or emergency situations. [ 16 ] [ 23 ]


Microsurgery  is utilized in many aspects of neurological surgery. Microvascular techniques are used in EC-IC bypass surgery and in restoration  carotid endarterectomy . The clipping of an aneurysm is performed under microscopic vision.  Minimally-invasive  spine surgery utilizes microscopes or endoscopes. Procedures such as microdiscectomy,  laminectomy , and artificial disc replacement rely on microsurgery. [ 24 ]


Using  stereotaxy  neurosurgeons can approach a minute target in the brain through a minimal opening. This is used in functional neurosurgery where electrodes are implanted or  gene therapy  is instituted with high level of accuracy as in the case of Parkinson's disease or Alzheimer's disease. Using the combination method of open and stereotactic surgery, intraventricular hemorrhages can potentially be evacuated successfully. [ 25 ]  Conventional surgery using image guidance technologies is also becoming common and is referred to as surgical navigation, computer-assisted surgery, navigated surgery, stereotactic navigation. Similar to a car or mobile Global Positioning System (GPS), image-guided surgery systems, like Curve Image Guided Surgery and StealthStation, use cameras or electromagnetic fields to capture and relay the patient's anatomy and the surgeon's precise movements in relation to the patient, to computer monitors in the operating room. These sophisticated computerized systems are used before and during surgery to help orient the surgeon with three-dimensional images of the patient's anatomy including the tumor. [ 40 ]  Real-time functional brain mapping has been employed to identify specific functional regions using  electrocorticography  (ECoG) [ 41 ]


Minimally invasive  endoscopic surgery  is commonly utilized by neurosurgeons when appropriate. Techniques such as  endoscopic endonasal surgery  are used in pituitary tumors,  craniopharyngiomas , chordomas, and the repair of cerebrospinal fluid leaks. Ventricular endoscopy is used in the treatment of intraventricular bleeds, hydrocephalus,  colloid cyst  and  neurocysticercosis . Endonasal endoscopy is at times carried out with neurosurgeons and ENT surgeons working together as a team. [ citation needed ]


Repair of craniofacial disorders and disturbance of cerebrospinal fluid circulation is done by neurosurgeons who also occasionally team up with maxillofacial and plastic surgeons. Cranioplasty for  craniosynostosis  is performed by pediatric neurosurgeons with or without plastic surgeons. [ 42 ]


Neurosurgeons are involved in  stereotactic radiosurgery  along with radiation oncologists in  tumor  and  AVM  treatment. Radiosurgical methods such as  Gamma knife ,  Cyberknife  and  Novalis Radiosurgery  are used as well. [ 43 ]


Endovascular neurosurgery  utilize endovascular image guided procedures for the treatment of  aneurysms , AVMs,  carotid stenosis , strokes, and spinal malformations, and vasospasms. Techniques such as  angioplasty , stenting, clot retrieval, embolization, and diagnostic angiography are endovascular procedures. [ 44 ]


A common procedure performed in neurosurgery is the placement of ventriculo-peritoneal shunt (VP shunt). In pediatric practice this is often implemented in cases of congenital  hydrocephalus . The most common indication for this procedure in adults is normal pressure hydrocephalus (NPH). [ 45 ]


Neurosurgery of the spine  covers the cervical, thoracic and lumbar spine. Some indications for spine surgery include spinal cord compression resulting from trauma, arthritis of the spinal discs, or spondylosis. In cervical cord compression, patients may have difficulty with gait, balance issues, and/or numbness and tingling in the hands or feet.  Spondylosis  is the condition of spinal disc degeneration and arthritis that may compress the spinal canal. This condition can often result in bone-spurring and  disc herniation . Power drills and special instruments are often used to correct any compression problems of the spinal canal. Disc herniations of spinal vertebral discs are removed with special  rongeurs .  This procedure is known as a  discectomy . Generally once a disc is removed it is replaced by an implant which will create a bony fusion between vertebral bodies above and below. Instead, a mobile disc could be implanted into the disc space to maintain mobility. This is commonly used in cervical disc surgery. At times instead of disc removal a Laser discectomy could be used to decompress a nerve root. This method is mainly used for lumbar discs.  Laminectomy  is the removal of the  lamina  of the vertebrae of the spine in order to make room for the compressed nerve tissue. [ 46 ]


Surgery for chronic pain is a sub-branch of functional neurosurgery. Some of the techniques include implantation of deep brain stimulators, spinal cord stimulators, peripheral stimulators and pain pumps. [ 47 ]


Surgery of the peripheral nervous system is also possible, and includes the very common procedures of carpal tunnel decompression and peripheral nerve transposition. Numerous other types of nerve entrapment conditions and other problems with the peripheral nervous system are treated as well. [ 48 ]


Conditions treated by neurosurgeons include, but are not limited to: [ 49 ]


Pain following brain surgery can be significant and may lengthen recovery, increase the amount of time a person stays in the hospital following surgery, and increase the risk of complications following surgery. [ 50 ]  Severe acute pain following brain surgery may also increase the risk of a person developing a chronic post- craniotomy  headache. [ 50 ]  Approaches to treating pain in adults include treatment with nonsteroidal anti‐inflammatory drugs ( NSAIDs ), which have been shown to reduce pain for up to 24 hours following surgery. [ 50 ]  Low-quality evidence supports the use of the medications  dexmedetomidine ,  pregabalin  or  gabapentin  to reduce post-operative pain. [ 50 ]  Low-quality evidence also supports scalp blocks and scalp infiltration to reduce postoperative pain. [ 50 ]   Gabapentin  or  pregabalin  may also decrease  vomiting  and  nausea  following surgery, based on very low-quality medical evidence. [ 50 ]


Neurosurgery is a part of practical  medicine  and the only specialty that involves invasive intervention in the activity of the living brain. The brain ensures the structural and functional integrity of the body and the implementation of all the main life processes of the body. Therefore, neurosurgery faces a wide range of bioethical issues and a significant selection of the latest  treatment  technologies. [ 54 ]


Neurosurgery has the following applied scientific and ethical problems:


Amygdalotomy , also known as  amygdalectomy , is a form of  psychosurgery  which involves the surgical removal or destruction of the  amygdala , or parts of the amygdala. It is usually a last-resort treatment for severe aggressive behavioral disorders and similar behaviors including hyperexcitability, violent outbursts, and self-mutilation. [ 1 ] [ 2 ] [ 3 ] [ 4 ]  The practice of medical amygdalotomy typically involves the administration of general anesthesia and is achieved through the application of cranial  stereotactic surgery  to target regions of the amygdala for surgical destruction. [ 3 ]  While some studies have found stereotactic amygdalotomy in humans to be an effective treatment for severe cases of intractable aggressive behavior that has not responded to standard treatment methods, [ 5 ] [ 6 ] [ 7 ] [ 8 ]  other studies remain inconclusive. [ 9 ] [ 10 ]  In most cases of amygdalotomy in humans, there is no substantial evidence of impairment in overall cognitive function, including intelligence and working memory, however, deficits in specific areas of memory have been noted pertaining to the recognition and emotional interpretation of facial stimuli.  This is because there are specialized cells in the amygdala which attend to facial stimuli.


The amygdala is considered to be an important underlying structure in the  fight-or-flight response , playing a mediating role in aggression in both humans and animals. [ 3 ]   Clinical studies have revealed that the stimulation of the amygdala produces or accentuates rageful behavior in animals. [ 4 ]  Research has also revealed that  lesions  of the amygdala in both humans and animals produces a calming effect on aggressive behavior. [ 3 ]  Based on these findings, amygdalotomy was developed as a neurosurgical procedure to ameliorate aggression by reducing arousal levels in the amygdala. [ 3 ] [ 11 ]


Since the early 1900s there has been an accumulation of experimental evidence to demonstrate the role of the  limbic system , specifically the amygdala complex in mediating emotional expressions of fear and anger. [ 11 ] [ 3 ]  Early primate studies have revealed that chemical and electrical stimulation of the amygdala region accentuates aggressive behavior. Conversely, destruction of the amygdala nucleus results in a taming effect of normal anger and fearing responses in primate behavior. Similarly, clinical studies in humans have revealed the close  etiological  role of temporal lobe structures, particularly the limbic system and the amygdala in mediating fear and rageful behavior. [ 3 ]  These findings have been instrumental in the development of clinical amygdalotomy as a form of neurosurgery to produce placating effects on abnormal aggressive behaviors. [ 11 ] [ 3 ]  Procedural amygdalotomy is used as a last recourse treatment for severe intractable aggression when other options including pharmacological treatments have been exhausted. The  psychopathology  of patients with severe aggressive behavior in clinical cases of amygdalotomy over the past 20th century vary, including  epileptics with violent convulsions, psychotics with violent outbursts, individuals with unmanageable conduct disorder, and patients with self-mutilative tendencies. The clinical practice of amygdalotomy in humans is commonly implemented under the stereotactic frame, with varying techniques used to destroy the amygdala, ranging from  radiofrequency , mechanical destruction and the injection of oil, wax, and alcohol. [ 3 ]  The preferred target zone of the amygdala also varies from basal and lateral nuclei, to the medial region, the cortico-medial group of nuclei and the bed of the  stria terminalis . [ 3 ]  The size of the lesion differs from one-third to one-half, to three-quarters, to the entire amygdalar region. [ 3 ]  In spite of these methodological differences, most published accounts of human amygdalotomy have indicated beneficial outcomes in reducing the intensity and frequency of aggressive behaviors. [ 3 ] [ 11 ]


Amongst some of the earliest studies conducted on the removal of the amygdala were animal and primate studies. [ 11 ] [ 3 ]  In the early 1890s, Friedrich Goltz conducted experiments on  temporal lobectomy  in dogs including the removal of the amygdala and found that dogs post-surgery experienced a taming effects on aggressive behaviors. [ 11 ]   Deep brain stimulation  studies in animals revealed that the temporal lobe is involved in mediating expressions of rage and aggression. [ 11 ]  A more detailed analysis of specific regions of the temporal lobe in animals revealed that the limbic system, specifically the amygdala complex, is involved in mediating fear and aggression. [ 11 ]  Some of the earliest primate studies on amygdalotomy were carried out on rhesus monkeys by Kluver and Bucy in the late 1930s. [ 11 ]  Data collected from these studies revealed that bilateral destruction of the amygdala resulted in a reduction in the intensity and frequency of fear and aggression behaviors.


The human counterpart of the role of the amygdala was then observed in the 20th century at the height of psychosurgery. [ 11 ]  Professor Hirotaro Narabayashi and his colleagues were the first researchers to carry out stereotactic amygdalotomy for the treatment of abnormal aggression and hyperexcitability in a series of 60 patients with psychological disturbances. [ 3 ] [ 11 ]  The procedure was performed under a stereotactic frame devised by Professor Narabayashi and involved the administration 0.6-0.8ml mixture of oil-wax to destroy the lateral groups of the amygdala nucleus, localized via  pneumoencephalography . [ 11 ]  The clinical results revealed a marked reduction in emotional disturbances amongst 85% of the cases. Following Narabayashi's study, there have been over 1000 cases of amygdalotomy reported in clinical trials as a last-resort treatment for severe intractable aggressive disorders. [ 3 ]  Around the same time, Hatai Chitanondh utilized a slightly different technique of stereotactic amygdalotomy using an injection of an olive oil mixture  to induce lesions to mechanically block signals in the amygdala. The results revealed an improvement in social adaptability of all seven patients. [ 11 ]  In the late 1960s and 1970s, Balasubramaniam and Ramamurthi investigated the largest clinical patient series to undergo stereotactic amygdalotomy for aggression behaviours. The procedure was performed via  high-frequency current generating electrodes inserted stereotactically to induce several small thermal lesions, creating a total lesion volume of 1800mm, a size that is larger than the amygdala. [ 11 ]  The improvement in maladaptive behavior in patients, including hyperexcitability, rebellious behavior, and destructive behavior, ranged from moderate to high. [ 11 ]  The development of  MRI  technology in the recent 20th century has enabled a more accurate and efficient process of amygdalotomy, with easier localization of amygdala regions during neuro-navigation as well as the use of advanced radiofrequency generating electrode to induce surgical lesions. [ 11 ]  Despite these recent advances in technology, there has been a decline in clinical cases of amygdalotomy for treatment of maladaptive behavior, with growing skepticism in the medical community of the cost-benefits of the procedure and partly due to a greater reliance on pharmacological treatments [ 11 ] [ 12 ]


There has been a general consensus amongst many researchers on the general effectiveness of amygdalotomy in reducing aggression amongst patients with psychosis, violent epilepsy, and self-mutilative behavior. [ 8 ] [ 7 ] [ 5 ]  A diverse study [ 8 ]  on stereotactic amygdalotomy used to treat 25 patients primarily for aggressive behavior and violent epilepsy, found that behavioral abnormalities were eliminated in 2 of the 20 patients, with a significant improvement in another 9 of the 20 patients with aggressive behavior manifests. Convulsions were also eliminated in 4 of the 21 patients, whilst 12 of the patients experienced a significant decrease in the number of epileptic convulsions. Patient rehabilitation was also effective with 2 of the 12 patients committed to mental institutions being discharged, whilst 5 of 8 patients awaiting institutionalization were no longer being considered. A multi-disciplinary project carried out on amygdalotomy amongst epileptics with violent outbursts found that amygdalotomy showed promising results, with a decline in violent, aggressive and anti-social behavior as well as a reduction amongst patients and an improvement in the occupational functioning of some of the patients. [ 4 ]  The researchers, however, concluded that the results cannot be generalized to non-epileptics. Other studies [ 5 ] [ 7 ]  conducted on patients with conduct disorder, personality disorder, self-mutilation, and schizophrenics with violent hallucinations found that these maladaptive behaviors also improved across these groups of patients. Using reliable and objective methods of evaluation, Heimburger and colleagues found that in patients who did not respond to non-surgical therapy, amygdalotomy was effective, with both conditions of uncontrolled conduct disorder and seizures seeming improved after surgery. [ 7 ]  Stereotaxic amygdalotomy conducted on 12 patients with schizophrenia and frequent self-mutilations found that, in 11 of the 12 patients, amygdalotomy resulted in elimination and or marked reduction of aggressive episodes. [ 5 ]  In two of patients with frequent self-mutilative episodes and reactive psychotic hallucinations, however, these symptoms disappeared only after an additional basofrontal tractotomy had been performed.


There is a scarcity of long-term studies on the follow-up effects of clinical amygdalotomy in humans. [ 3 ]  Amongst the few follow-up studies, includes a research study [ 6 ]  which compared the results of clinical amygdalotomy in 58 patients pre and post-surgery over an average of 6 years using objective analysis such as psychiatric interviews, neuropsychological tests and  EEG analysis  and found no indication of worsening of symptoms. Additionally, the researchers found some evidence for the retention of positive outcomes in one-third of the patients, which were not limited to improvements in rageful behaviour but also included a decrease in the overall frequency of seizures. Another follow-up study [ 13 ]  by Professor Narabayashi and colleagues observed the clinical effects of amygdalotomy in 40 cases from 3 to 5 years and found 27 of the cases had continued a satisfactory improvement in calming and taming effects on what was previously uncontrollable aggression including destructive and violent behaviour.


In most cases of amygdalotomy in humans, there is no substantial evidence of impairment in overall cognitive function, including intelligence and working memory. [ 10 ] [ 9 ]  However, deficits in specific areas of memory have been noted, particularly areas of memory pertaining to the recognition and emotional interpretation of facial stimuli. [ 10 ]   These findings of face recognition impairment after amygdalotomy are of particular importance due to the neurophysiological data collected on the importance of cells in the amygdala that specifically attend to facial stimuli in both humans and primates. [ 10 ]  A detailed case study of a patient who had undergone a bilateral amygdalotomy found incidences where the patient showed poor learning of new faces and impaired recognition of familiar faces, particularly troubles with naming faces. [ 10 ]  Additionally the patient also revealed further deficits in the emotional processing of facial stimuli, demonstrating difficulty in identifying and matching a range of facial expressions. Another study of 15 patients showed no reduction in general intelligence, but there was a similar pattern of changes in attention and memory involving facial stimuli. This link between the amygdala and social disturbances pertaining to the processing of facial stimuli has been investigated as a possible side-effect of amygdalotomy in some patients [ 10 ] [ 9 ]


Atypical trigeminal neuralgia  ( ATN ), or  type 2 trigeminal neuralgia , is a form of  trigeminal neuralgia , a disorder of the  fifth cranial nerve .  This form of  nerve pain  is difficult to diagnose, as it is rare and the symptoms overlap with several other disorders. [ 1 ]  The symptoms can occur in addition to having  migraine  headache, or can be mistaken for migraine alone, or dental problems such as  temporomandibular joint disorder  or musculoskeletal issues. ATN can have a wide range of symptoms and the  pain  can fluctuate in intensity from mild aching to a crushing or burning sensation, and also to the extreme pain experienced with the more common trigeminal neuralgia.


ATN pain can be described as heavy, aching, stabbing, and burning. Some patients have a constant migraine-like headache.  Others may experience intense pain in one or in all three trigeminal nerve branches, affecting teeth, ears, sinuses, cheeks, forehead,  upper and lower jaws, behind the eyes, and scalp. In addition, those with ATN may also experience the shocks or stabs found in type 1 TN. [ citation needed ]


Many TN and ATN patients have pain that is "triggered" by light touch on shifting trigger zones. ATN pain tends to worsen with talking, smiling, chewing, or in response to sensations such as a cool breeze. The pain from ATN is often continuous, and periods of remission are rare. Both TN and ATN can be bilateral, though the character of pain is usually different on the two sides at any one time. [ 2 ]


ATN is usually attributed to inflammation or  demyelination , with increased sensitivity of the  trigeminal nerve . These effects are believed to be caused by infection, demyelinating diseases, or compression of the trigeminal nerve (by an impinging vein or artery, a tumor, dental trauma, accidents, or  arteriovenous malformation ) and are often confused with dental problems. Though TN and ATN most often present in the fifth decade, cases have been documented as early as infancy. [ citation needed ]


Both forms of facial neuralgia are relatively rare, with an incidence recently estimated between 12 and 24 new cases per hundred thousand population per year. [ 3 ] [ 4 ]


ATN often goes undiagnosed or misdiagnosed for extended periods, leading to a great deal of unexplained pain and anxiety. A National Patient Survey conducted by the US Trigeminal Neuralgia Association in the late 1990s indicated that the average facial neuralgia patient may see six different physicians before receiving a first definitive diagnosis.  The first practitioner to see facial neuralgia patients is often a dentist who may lack deep training in facial neurology. Thus ATN may be misdiagnosed as Temporomandibular Joint Disorder. [ 5 ]


This disorder is regarded by many medical professionals to comprise the most severe form of chronic pain known in medical practice. In some patients, pain may be unresponsive even to opioid drugs at any dose level that leaves the patient conscious. The disorder has thus acquired the unfortunate and possibly inflammatory nickname, "the suicide disease". [ 6 ]


Symptoms of ATN may overlap with a pain disorder occurring in teeth called  atypical odontalgia  (literal meaning "unusual tooth pain"), with aching, burning, or stabs of pain localized to one or more teeth and adjacent jaw. The pain may seem to shift from one tooth to the next, after root canals or extractions. In desperate efforts to alleviate pain, some patients undergo multiple (but unneeded) root canals or extractions, even in the absence of suggestive X-ray evidence of  dental abscess . [ citation needed ]


ATN symptoms may also be similar to those of post-herpetic neuralgia, which causes nerve inflammation when the latent herpes zoster virus of a previous case of chicken pox re-emerges in shingles. Fortunately, post-herpetic neuralgia is generally treated with medications that are also the first medications tried for ATN, which reduces the negative impact of misdiagnosis. [ citation needed ]


The subject of atypical trigeminal neuralgia is considered problematic even among experts.  The term atypical TN is broad and due to the complexity of the condition, there are considerable issues with defining the condition further. Some medical practitioners no longer make a distinction between facial neuralgia (a nominal condition of inflammation) versus facial neuropathy (direct physical damage to a nerve). [ citation needed ]


Due to the variability and imprecision of their pain symptoms, ATN or atypical odontalgia patients may be misdiagnosed with  atypical facial pain  (AFP) or "hypochondriasis", both of which are considered problematic by many practitioners. [ 7 ]  The term "atypical facial pain" is sometimes assigned to pain which crosses the mid-line of the face or otherwise does not conform to expected boundaries of nerve distributions or characteristics of validated medical entities. As such, AFP is seen to comprise a diagnosis by reduction. [ citation needed ]


As noted in material published by the [US] National Pain Foundation: "atypical facial pain is a confusing term and should never be used to describe patients with trigeminal neuralgia or trigeminal neuropathic pain. Strictly speaking, AFP is classified as a "somatiform pain disorder"; this is a psychological diagnosis that should be confirmed by a skilled pain psychologist. Patients with the diagnosis of AFP have no identifiable underlying physical cause for the pain. The pain is usually constant, described as aching or burning, and often affects both sides of the face (this is almost never the case in patients with trigeminal neuralgia). The pain frequently involves areas of the head, face, and neck that are outside the sensory territories that are supplied by the trigeminal nerve. It is important to correctly identify patients with AFP since the treatment for this is strictly medical. Surgical procedures are not indicated for atypical facial pain." [ 8 ]   [ citation needed ]


The term "hypochondriasis" is closely related to "somatoform pain disorder" and "conversion disorder" in the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association.  As of July 2011, this axis of the DSM-IV is undergoing major revision for the DSM-V, with introduction of a new designation "Complex Somatic Symptom Disorder". However, it remains to be demonstrated that any of these "disorders" can reliably be diagnosed as a medical entity with a discrete and reliable course of therapy. [ 9 ] [ 10 ] [ 11 ] [ 12 ]


It is possible that there are triggers or aggravating factors that patients need to learn to recognize to help manage their health. Bright lights, sounds, stress, and poor diet are examples of additional stimuli that can contribute to the condition. The pain can cause nausea, so beyond the obvious need to treat the pain, it is important to be sure to try to get adequate rest and nutrition.


Depression is frequently co-morbid with neuralgia and neuropathic pain of all sorts, as a result of the negative effects that pain has on one's life. Depression and chronic pain may interact, with chronic pain often predisposing patients to depression, and depression operating to sap energy, disrupt sleep and heighten sensitivity and the sense of suffering.  Dealing with depression should thus be considered equally important as finding direct relief from the pain. [ 13 ]


Diagnosis for ATN is more difficult and complex than typical TN. However, the diagnosis for ATN can be supported by a positive response to a low dose of tricyclic antidepressant medications (such as amitriptyline or nortriptyline), similar to neuropathic pain diagnoses. [ citation needed ] [ 14 ]


Treatment of people believed to have ATN or TN is usually begun with medication.  The long-time first drug of choice for facial neuralgia has been  carbamazepine , an  anti-seizure agent . Due to the significant side-effects and hazards of this drug, others have recently come into common use as alternatives. These include  oxcarbazepine ,  lamotrigine , and  gabapentin .  A positive patient response to one of these medications might be considered as supporting evidence for the diagnosis, which is otherwise made from medical history and pain presentation.  There are no present medical tests to conclusively confirm TN or ATN. [ citation needed ]


If the anti-seizure drugs are found ineffective, one of the  tricyclic antidepressant  medications, such as  amitriptyline  or  nortriptyline , may be used. The tricyclic antidepressants are known to have dual action against both depression and neuropathic pain.  Other drugs which may also be tried, either individually or in combination with an anti-seizure agent, include  baclofen ,  pregabalin , and opioid drugs such as  oxycodone  or an oxycodone/paracetamol combination. [ citation needed ]


For some people with ATN  opioids  may represent the only viable medical option which preserves quality of life and personal functioning.  Although there is considerable controversy in public policy and practice in this branch of medicine, practice guidelines have long been available and published. [ 15 ] [ 16 ] [ 17 ]


If drug treatment is found to be ineffective or causes disabling side effects, one of several  neurosurgical  procedures may be considered. The available procedures are believed to be less effective with type II (atypical) trigeminal neuralgia than with type I (typical or "classic") TN. Among present procedures, the most effective and long lasting has been found to be  microvascular decompression  (MVD), which seeks to relieve direct compression of the trigeminal nerve by separating and padding blood vessels in the vicinity of the emergence of this nerve from the brain stem, below the cranium. [ 18 ]


Choice of a surgical procedure is made by the doctor and patient in consultation, based on the patient's pain presentation and health and the doctor's medical experience.  Some neurosurgeons resist the application of MVD or other surgeries to atypical trigeminal neuralgia, in light of a widespread perception that ATN pain is less responsive to these procedures.  However, recent papers suggest that in cases where pain initially presents as type I TN, surgery may be effective even after the pain has evolved into type II. [ 19 ]


An  auditory brainstem implant  ( ABI ) is a surgically implanted electronic device that provides a sense of sound to a person who is profoundly deaf, due to retrocochlear hearing impairment (due to illness or injury damaging the  cochlea  or  auditory nerve , and so precluding the use of a  cochlear implant ). In Europe, ABIs have been used in children and adults, and in patients with  neurofibromatosis type II . [ 1 ]


The auditory brainstem implant was first developed in 1979 by  William F. House , a  neuro-otologist  associated with the  House Ear Institute , for patients with  neurofibromatosis type 2  (NF2). House's original ABI consisted of two ball electrodes that were implanted near the surface of the  cochlear nucleus  on the  brainstem . In 1997, Robert Behr at the  University of Wurzburg ,  Germany , performed an ABI implantation using a 12- electrode array  implant with an audio processor based on the  MED-EL  C40+ cochlear implant. [ 2 ]  The first pediatric ABI implantation was performed by Vittorio Colletti from  Verona ,  Italy , in 1999. [ 3 ]


In contrast to cochlear implants, ABI implantation is relatively rare. By 2010, there were only 500 patients worldwide who had undergone implantation. [ 4 ]


An ABI system consists of an internal part (the implant) and an external part (the audio processor or sound processor). It is similar in design and function to a cochlear implant.


The external audio processor is worn on or behind the  ear . It contains at least one  microphone , which picks up sound signals from the environment. The audio processor converts these signals into digital signals and sends them to the coil. The coil transmits the signals through the  skin  to the implant below. [ 5 ]


The internal implant sends the signals to the electrode array. The design of the electrode array is the key difference between a cochlear implant and an ABI. Whereas the electrode array for a CI is wire-shaped and is inserted into the  cochlea , the electrode array of an ABI is paddle-shaped and is placed on the cochlear nucleus of the brainstem. [ 3 ]  By stimulating the brainstem, the ABI sends the sound signals to the brain, allowing the patient to perceive sound. [ 5 ]


Until 2018, ABI was only indicated for patients with Neurofibromatosis Type 2 (NF2). NF2 is a genetic disorder that is characterised by the development of non-cancerous tumours along the nervous system. These  vestibular schwannomas  (also known as acoustic neuromas) often form on the  auditory nerve , and surgical removal of these NF2 tumours can damage the auditory nerve and limiting the patient's ability to hear. [ 6 ]


NF2 generally presents in adolescence or young adulthood, so candidacy was previously limited to patients aged 15 years or older, with NF2 and bilateral non-functioning auditory nerves. [ 6 ]


In Europe and other countries, ABI is CE-marked and approved for patients 12 months and older who cannot benefit from a cochlear implant due to non-functional auditory nerves. This includes both  congenital  and accrued  etiologies , including:


The US  FDA  approved clinical trials of ABIs for children in 2013. [ 3 ]  A handful of medical centres, including  New York University , are undergoing feasibility studies in the pediatric population. [ 3 ]


ABI implantation requires a  craniotomy  and is therefore much more complex than CI surgery. It is normally performed by both a  neurosurgeon  and an ENT surgeon together, who insert the electrode array through the  fourth ventricle  onto the surface of the cochlear nucleus. [ 3 ]


For patients with NF2, the surgeon will spend a significant amount of time removing the acoustic neuroma tumours before inserting the implant.  Depending upon the surgical approach, this may involve sacrificing the auditory nerve, thus rendering the patient deaf. [ 3 ]  Patients with NF2, who undergo both tumour removal and implantation in the same surgery, generally experience a longer post-op stay than patients without NF2. [ 3 ]


Speech perception outcomes with an ABI are generally poorer than those reported in cochlear implant multichannel CI users. Most patients are able to detect the presence of environmental sounds and speech. [ 3 ]  Speech understanding gradually improves during the first three years after activation, and most patients experience better speech understanding using a combination of lip-reading and the ABI, as opposed to lip-reading alone. However, most patients are unable to understand speech using only their ABI. [ 7 ]


There are two reasons that could explain the difference in outcomes between cochlear implants and ABIs. Firstly, non-auditory side-effects, such as  vertigo , limit the overall number of electrodes that can deliver useful frequency information. Electrodes found to cause one of these side-effects are deactivated, resulting in fewer signals reaching the brain. In addition, the brainstem is unable to offer the same tonotopic range as the cochlea. With a cochlear implant, the electrodes positioned in the basal end of the cochlea elicit a higher pitch sensation than those positioned in the apical end. In contrast, the tonotopic map within the cochlear nucleus runs parallel and obliquely through the nucleus and the ABI positioned on the surface does not stimulate neural structures in such a clear, tonotopically ordered way. This makes it harder to achieve optimal results during fitting. [ 7 ]


Patients without NF2 tend to experience better speech outcomes with an ABI than those with NF2. [ 7 ]  A study by Colletti found that a significant number of patients without NF2 were able to understand speech with an ABI, including effortless telephone use. [ 8 ]  It is believed that the tumours caused by the NF2 damage specialised cells in the cochlear nucleus important for speech perception. [ 7 ]


There is some evidence to suggest that ABI can help to reduce the effect of tinnitus and improve quality of life. [ 9 ]  Better language outcomes are also expected with younger children implanted before the age of 2. [ 10 ]  Because of the wide range of possible outcomes, it is crucial that patients and/or their parents are counselled effectively about what they can realistically expect from an ABI. Parents are advised about additional communication modalities available, such as the use of sign language, as the ultimate goal is to facilitate language with the child. [ 3 ]


Brain mapping  is a set of  neuroscience  techniques predicated on the mapping of (biological) quantities or properties onto spatial representations of the (human or non-human)  brain  resulting in  maps .


According to the definition established in 2013 by  Society for Brain Mapping and Therapeutics  (SBMT), brain mapping is specifically defined, in summary, as the study of the  anatomy  and function of the brain and  spinal cord  through the use of  imaging ,  immunohistochemistry ,  molecular  &  optogenetics ,  stem cell  and  cellular biology ,  engineering ,  neurophysiology  and  nanotechnology .


In 2024, a team of 287 researchers completed a full brain mapping of an adult animal (a  Drosophila melanogaster , or fruit fly) and published their results in  Nature . [ 1 ] [ 2 ]


All  neuroimaging  is considered part of brain mapping. Brain mapping can be conceived as a higher form of neuroimaging, producing brain images supplemented by the result of additional (imaging or non-imaging) data processing or analysis, such as maps projecting (measures of) behavior onto brain regions (see  fMRI ). One such map, called a  connectogram , depicts cortical regions around a circle, organized by lobes. Concentric circles within the ring represent various common neurological measurements, such as cortical thickness or curvature. In the center of the circles, lines representing white matter fibers illustrate the connections between cortical regions, weighted by  fractional anisotropy  and strength of connection. [ 3 ]  At higher resolutions brain maps are called  connectomes . These maps incorporate individual neural connections in the brain and are often presented as  wiring diagrams . [ 4 ]


Brain mapping techniques are constantly evolving, and rely on the development and refinement of image acquisition, representation, analysis, visualization and interpretation techniques. [ 5 ]   Functional and structural neuroimaging are at the core of the mapping aspect of brain mapping.


Some scientists have criticized the brain image-based claims made in  scientific journals  and the popular press, like the discovery of "the part of the brain responsible" things like love or musical abilities or a specific memory.  Many mapping techniques have a relatively low resolution, including hundreds of thousands of neurons in a single  voxel .  Many functions also involve multiple parts of the brain, meaning that this type of claim is probably both unverifiable with the equipment used, and generally based on an incorrect assumption about how brain functions are divided.  It may be that most brain functions will only be described correctly after being measured with much more fine-grained measurements that look not at large regions but instead at a very large number of tiny individual  brain circuits .  Many of these studies also have technical problems like small sample size or poor equipment calibration which means they cannot be reproduced - considerations which are sometimes ignored to produce a sensational journal article or news headline.  In some cases the brain mapping techniques are used for commercial purposes,  lie detection , or medical diagnosis in ways which have not been scientifically validated. [ 6 ] [ page needed ]


In the late 1980s in the United States, the Institute of Medicine of the National Academy of Science was commissioned to establish a panel to investigate the value of integrating neuroscientific information across a variety of techniques. [ 7 ] [ page needed ]


Of specific interest is using structural and  functional magnetic resonance imaging  (fMRI),  diffusion MRI  (dMRI),  magnetoencephalography  (MEG), electroencephalography ( EEG ),  positron emission tomography  (PET),  Near-infrared spectroscopy  (NIRS)  and other non-invasive scanning techniques to map  anatomy ,  physiology ,  perfusion , function and  phenotypes  of the human brain. Both healthy and  diseased  brains may be mapped to study  memory ,  learning ,  aging , and  drug  effects in various populations such as people with  schizophrenia ,  autism , and  clinical depression . This led to the establishment of the  Human Brain Project . [ 8 ] [ page needed ]   It may also be crucial to understanding traumatic brain injuries (as in the case of  Phineas Gage ) [ 9 ]  and improving brain injury treatment. [ 10 ] [ 11 ]


Following a series of meetings, the International Consortium for Brain Mapping (ICBM) evolved. [ 12 ] [ page needed ]   The ultimate goal is to develop flexible computational  brain atlases .


The interactive and citizen science website  Eyewire  maps mices' retinal cells and was launched in 2012. In 2021, the most comprehensive 3D map of the human brain was published by researchers at  Google . It shows neurons and their connections along with blood vessels and other components of a millionth of a brain. For the map, the 1 mm³ sized fragment was sliced into about 5,300 pieces of about 30  nanometer  thickness which were then each scanned with an  electron microscope . The interactive map required 1.4  petabytes  of storage-space. [ 14 ] [ 15 ]  About two months later, scientists reported that they created the first complete neuron-level-resolution 3D map of a monkey brain which they scanned via a new method within 100 hours. They made only a fraction of the 3D map publicly available as the entire map takes more than 1 petabyte of storage space even when compressed. [ 16 ] [ 17 ]


In October 2021, the BRAIN Initiative Cell Census Network concluded the first phase of a long-term project to generate an atlas of the entire mouse (mammalian) brain with 17 studies, including an atlas and census of cell types in the  primary motor cortex . [ 18 ] [ 19 ] [ 20 ]


In 2024, FlyWire, a team of 287 researchers spanning 76 institutions completed a brain mapping, or connectome, of an adult animal (a  Drosophila melanogaster , or fruit fly) and published their results in  Nature . [ 1 ]  Prior to this, the only adult animal to have its brain entirely reconstructed was the nematode  Caenorhabditis elegans , but the fruit fly brain map is the first "complete map of any complex brain", according to Murthy, one of the researchers involved. [ 2 ]  Primary mapping data was collected through  electron microscopy , assisted by  artificial intelligence  and  citizen scientists , who corrected errors that artificial intelligence made. The resulting model had more than 140,000 neurons with over 50 million synapses. [ 21 ]  From the model, research expect to identify how the brain creates new connections for functions such as vision, creating  digital twin  equivalents to track how segments of the neuron connection map interact to external signals, including the nervous system. [ 22 ]


In 2021, the first connectome that shows how an animal's brain changes throughout its lifetime was reported. Scientists mapped and compared the whole brains of eight isogenic  C. elegans  worms, each at a different stage of development. [ 23 ] [ 24 ]  Later that year, scientists combined electron microscopy and brainbow imaging to show for the first time the development of a mammalian neural circuit. They reported the complete wiring diagrams between the CNS and muscles of ten individual mice. [ 25 ]


In August 2021, scientists of the  MICrONS  program, launched in 2016, [ 26 ]  published a functional connectomics dataset that "contains calcium imaging of an estimated 75,000 neurons from primary visual cortex (VISp) and three higher visual areas (VISrl, VISal and VISlm), that were recorded while a mouse viewed natural movies and parametric stimuli". [ 27 ] [ 28 ]  Based on this data they also published "interactive visualizations of anatomical and functional data that span all 6 layers of mouse primary visual cortex and 3 higher visual areas (LM, AL, RL) within a cubic millimeter volume" – the  MICrONS Explorer . [ 29 ]


In 2022, a first spatiotemporal cellular atlas of the  axolotl  brain development and  regeneration , the interactive  Axolotl Regenerative Telencephalon Interpretation via Spatiotemporal Transcriptomic Atlas  , revealed key insights about axolotl  brain regeneration . [ 30 ] [ 31 ]


A  brain transplant  or  whole-body transplant  is a procedure in which the brain of one organism is transplanted into the body of another organism. It is a procedure distinct from  head transplantation , which involves transferring the entire head to a new body, as opposed to the brain only. Theoretically, a person with complete organ failure could be given a new and functional body while keeping their own personality, memories, and consciousness through such a procedure.  Neurosurgeon   Robert J. White  has grafted the head of a monkey onto the headless body of another monkey. EEG readings showed the brain was later functioning normally. Initially, it was thought to prove that the brain was an  immunologically privileged  organ, as the host's immune system did not attack it at first, [ 1 ]  but immunorejection caused the monkey to die after nine days. [ 2 ]  Brain transplants and similar concepts have also been explored in various forms of science fiction.


One of the most significant barriers to the procedure is the inability of  nerve  tissue to heal properly;  scarred  nerve tissue does not transmit signals well, which is why  spinal cord injuries  devastate muscle function and sensation.


Alternatively, a  brain–computer interface  can be used connecting the subject to their own body. A study [ 3 ]  using a monkey as a subject shows that it is possible to directly use commands from the brain, bypass the spinal cord and enable hand function. An advantage is that this interface can be adjusted after the surgical interventions are done where nerves can not be reconnected without surgery.


Also, for the procedure to be practical, the age of the donated body must be close to that of the recipient brain: an adult brain cannot fit into a skull that has not reached its full growth, which occurs at age 9–12 years.


When organs are transplanted, aggressive  transplant rejection  by the host's  immune system  can occur. Because immune cells of the CNS contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood, the brain has been hypothesized to be an  immunologically privileged  (unrejectable) organ. [ 4 ] [ 5 ] [ 6 ]  However, immunorejection of a functional transplanted brain has been reported in monkeys. [ 7 ]


In 1982, Dr. Dorothy T. Krieger, chief of  endocrinology  at  Mount Sinai Medical Center  in New York City, achieved success with a partial brain transplant in mice. [ 8 ]


In 1998, a team of  surgeons  from the  University of Pittsburgh Medical Center  attempted to transplant a group of  brain cells  to Alma Cerasini, who had suffered a severe  stroke  that caused the loss of mobility in her right  limbs  as well as had limited speech. The team hoped that the cells would correct the listed damage. She died later on. [ 9 ]


The whole-body transplant is just one of several means of putting a consciousness into a new body that have been explored in  science fiction . [ 10 ]


In the film  Get Out  (2017), written and directed by  Jordan Peele , a white woman ( Allison Williams ) lures her black boyfriend ( Daniel Kaluuya ) to her family's estate to be auctioned off for a brain transplant procedure that enables older white people to obtain pseudo-immortality in a black person's body.


In the film  Pichaikkaran 2  (2023), written and directed by  Vijay Antony , a CEO and his accomplice transplanted a beggar's brain to an ultra-rich man to rob him of his wealth.


In  Maxwell Atoms ' Cartoon Network series  Evil Con Carne  (2003–2004), Hector Con Carne was reduced to a brain and a stomach and both of them were put in jars attached to the body of a Russian circus bear. Hector's brain is the main character of the cartoon.


Edgar Rice Burroughs'  The Mastermind of Mars  involves a surgeon who performs brain transplants as his main operation, as well as a man from Earth—the narrator and main character—who is also trained to perform brain transplants.


In  Neil R. Jones '  Professeur Jameson  stories (1931), the main character is the last earthman, whose brain is saved by some alien cyborgs called the Zoromes, and is inserted into a robotic body, making him immortal.


Robert Heinlein's 1970 science fiction novel,  I Will Fear No Evil , features a main character named Johann Sebastian Bach Smith whose entire brain is transplanted into his deceased secretary's skull.


In the horror film  The Skeleton Key , the protagonist, Caroline, discovers that the old couple she is looking after are poor Voodoo witch doctors who stole the bodies of two young, privileged children in their care using a ritual which allows a soul to swap bodies. Unfortunately the evil old couple also trick Caroline and their lawyer into the same procedure, and both end up stuck in old dying bodies unable to speak while the witch doctors walk off with their young bodies.


In  Anne Rice 's  The Tale of the Body Thief , the vampire Lestat discovers a man, Raglan James, who can will himself into another person's body.  Lestat demands that the procedure be used on him to allow him to be human once again, but soon finds that he has made an error and is forced to recapture James in his vampiric form so he can take his body back.


In  JoJo's Bizarre Adventure  (part 3:  Stardust Crusaders ), Dio Brando, a vampire who was the main antagonist in the first part of JJBA, comes back from his 100-year sleep with his new body of Jonathan Joestar. He was only left with his head, so he took the body of Jonathan from the neck down.


In Matthew Broughton's BBC radio drama thriller  Tracks  (series 1 –  Origins ), the protagonist Helen Ash discovers that many of the victims in a plane crash which she witnessed have vital organs missing or deficient, including the brain. She goes on to uncover her estranged father's murky and secretive past and her own connection.


In the horror game  SOMA , the protagonist's brain is scanned in extreme detail for medical purposes; over a century later, the data from the scan are transferred into an artificial body, effectively performing a consciousness transplant. Later in the story, the protagonist comes across many other cases of a similar event, with far worse body choices for the transplanted consciousnesses. The Protagonist's goal is to ensure that an artificial world called the "ARK" is as safe as possible. The ARK is a supercomputer, a server hosting a virtual world, which can be explored with one's consciousness alone. Many people, including the protagonist, have had their brains scanned and consciousnesses "transplanted" into the computer, so that they may live on, since Earth is no longer habitable in SOMA's story.


Similar in many ways to this is the idea of  mind uploading , promoted by  Marvin Minsky  and others with a mechanistic view of natural intelligence and an optimistic outlook regarding  artificial intelligence .  It is also a goal of  Raëlism , a small cult based in Florida, France, and Quebec.  While the ultimate goal of transplanting is transfer of the brain to a new body optimized for it by  genetics ,  proteomics , and/or other medical procedures, in uploading the brain itself moves nowhere and may even be physically destroyed or discarded; the goal is rather to duplicate the information patterns contained within the brain.


Another similar literary theme, though different from either procedure described above, is the transplanting of a human brain into an artificial, usually robotic, body.  Examples of this include:  Caprica ;  Ghost in the Shell ;  RoboCop ; the  DC Comics  superhero  Robotman ; the  Cybermen  from the  Doctor Who  television series; the  cymeks  in the  Legends of Dune  series; Dr. Light and Dr. Wily in the  Mega Man  Series, in which their consciousnesses are seen living on a century after through program data in the  Mega Man X  series; as full-body cyborgs in many  manga  or works in the  cyberpunk  genre.  In one episode of  Star Trek ,  Spock's Brain  is stolen and installed in a large computer-like structure; and in " I, Mudd " Uhura is offered immortality in an android body. The novel  Harvest of Stars  by  Poul Anderson  features many central characters who undergo such transplants, and deals with the difficult decisions facing a human contemplating such a procedure. In the  Star Wars  expanded universe  the shadow droids were created by taking the brains of grievously wounded  TIE fighter  pilot aces. After surgically transplanting them into a protective cocoon filled with nutrient fluids, they were surgically connected to cybernetic hardware that gave them external sensors, flight control, and tactical computers that augmented their reflexes beyond the biological limit, at the cost of their humanity. Emperor  Palpatine  also imbued them with the dark side giving them a sixth sense, and making them into extensions of his own will.


An  intracranial aneurysm , also known as a  cerebral aneurysm , is a  cerebrovascular disorder  characterized by a localized dilation or ballooning of a  blood vessel  in the brain due to a weakness in the vessel wall. These  aneurysms  can occur in any part of the brain but are most commonly found in the arteries of the cerebral arterial circle. The risk of rupture varies with the size and location of the aneurysm, with those in the posterior circulation being more prone to rupture.


Cerebral aneurysms are classified by size into small, large, giant, and super-giant, and by shape into saccular (berry),  fusiform , and microaneurysms. Saccular aneurysms are the most common type and can result from various risk factors, including genetic conditions,  hypertension ,  smoking , and  drug abuse .


Symptoms of an unruptured aneurysm are often minimal, but a ruptured aneurysm can cause severe  headaches ,  nausea ,  vision impairment , and  loss of consciousness , leading to a  subarachnoid hemorrhage . Treatment options include surgical clipping and endovascular coiling, both aimed at preventing further bleeding.


Diagnosis typically involves imaging techniques such as  CT  or  MR angiography  and lumbar puncture to detect subarachnoid hemorrhage. Prognosis depends on factors like the size and location of the aneurysm and the patient’s age and health, with larger aneurysms having a higher risk of rupture and poorer outcomes.


Advances in medical imaging have led to increased detection of unruptured aneurysms, prompting ongoing research into their management and the development of predictive tools for rupture risk.


Cerebral aneurysms are classified both by size and shape. Small aneurysms have a diameter of less than 15 mm. Larger aneurysms include those classified as large (15 to 25 mm), giant (25 to 50 mm) (0.98 inches to 1.97 inches), and super-giant (over 50 mm). [ 3 ]


Saccular aneurysms, also known as berry aneurysms, appear as a round outpouching and are the most common form of cerebral aneurysm. [ 3 ] [ 4 ]  Causes include connective tissue disorders,  polycystic kidney disease , arteriovenous malformations, untreated  hypertension , tobacco smoking, cocaine and amphetamines, intravenous drug abuse (can cause infectious mycotic aneurysms), alcoholism, heavy caffeine intake, head trauma, and infection in the arterial wall from  bacteremia  (mycotic aneurysms). [ 5 ]


Fusiform  dolichoectatic  aneurysms represent a widening of a segment of an artery around the entire blood vessel, rather than just arising from a side of an artery's wall. They have an estimated annual risk of rupture between 1.6 and 1.9 percent. [ 6 ] [ 7 ]


Microaneurysms, also known as  Charcot–Bouchard aneurysms , typically occur in small  blood vessels  (less than 300  micrometre  diameter), most often the  lenticulostriate  vessels of the  basal ganglia , and are associated with  chronic   hypertension . [ 8 ]  Charcot–Bouchard aneurysms are a common cause of  intracranial hemorrhage . [ 9 ]


A small, unchanging aneurysm will produce few, if any, symptoms. Before a larger aneurysm ruptures, the individual may experience such symptoms as a sudden and unusually severe headache,  nausea , vision impairment,  vomiting , and  loss of consciousness , or no symptoms at all. [ 10 ]


If an aneurysm ruptures, blood leaks into the space around the brain. This is called a  subarachnoid hemorrhage . Onset is usually sudden without  prodrome , classically presenting as a " thunderclap headache " worse than previous headaches. [ 11 ] [ 12 ]  Symptoms of a subarachnoid hemorrhage differ depending on the site and size of the aneurysm. [ 12 ]  Symptoms of a ruptured aneurysm can include: [ 13 ]


Almost all aneurysms rupture at their apex. This leads to hemorrhage in the subarachnoid space and sometimes in brain  parenchyma . Minor leakage from aneurysm may precede rupture, causing warning headaches. About 60% of patients die immediately after rupture. [ 14 ]  Larger aneurysms have a greater tendency to rupture, though most ruptured aneurysms are less than 10 mm in diameter. [ 12 ]


A ruptured microaneurysm may cause an  intracerebral hemorrhage , presenting as a focal neurological deficit. [ 12 ]


Rebleeding,  hydrocephalus  (the excessive accumulation of  cerebrospinal fluid ),  vasospasm  (spasm, or narrowing, of the blood vessels), or multiple aneurysms may also occur. The risk of rupture from a cerebral aneurysm varies according to the size of an aneurysm, with the risk rising as the aneurysm size increases. [ 15 ]


Vasospasm , referring to blood vessel constriction, can occur secondary to subarachnoid hemorrhage following a ruptured aneurysm. This is most likely to occur within 21 days and is seen radiologically within 60% of such patients. The vasospasm is thought to be secondary to the  apoptosis  of  inflammatory  cells such as  macrophages  and  neutrophils  that become trapped in the subarachnoid space. These cells initially invade the subarachnoid space from the circulation in order to  phagocytose  the hemorrhaged red blood cells. Following apoptosis, it is thought there is a massive degranulation of vasoconstrictors, including  endothelins  and  free radicals , that cause the vasospasm. [ 16 ]


Intracranial aneurysms may result from diseases acquired during life, or from genetic conditions.   Hypertension ,  smoking ,  alcoholism , and  obesity  are associated with the development of brain aneurysms. [ 11 ] [ 12 ] [ 17 ]   Cocaine  use has also been associated with the development of intracranial aneurysms. [ 12 ]


Other acquired associations with intracranial aneurysms include head trauma and infections. [ 11 ]


Coarctation of the aorta is also a known risk factor, [ 11 ]  as is  arteriovenous malformation . [ 14 ]  Genetic conditions associated with  connective tissue disease  may also be associated with the development of aneurysms. [ 11 ]  This includes: [ 18 ]


Specific genes have also had reported association with the development of intracranial aneurysms, including  perlecan ,  elastin ,  collagen  type 1 A2, endothelial  nitric oxide synthase ,  endothelin  receptor A and  cyclin dependent kinase inhibitor . Recently, several  genetic loci  have been identified as relevant to the development of intracranial aneurysms. These include 1p34–36, 2p14–15, 7q11, 11q25, and 19q13.1–13.3. [ 19 ]


Aneurysm  means an outpouching of a  blood vessel  wall that is filled with blood. Aneurysms occur at a point of weakness in the vessel wall. This can be because of acquired disease or hereditary factors. The repeated trauma of blood flow against the vessel wall presses against the point of weakness and causes the aneurysm to enlarge. [ 20 ]  As described by the  law of Young-Laplace , the increasing area increases tension against the aneurysmal walls, leading to enlargement. [ 21 ] [ 22 ] [ 23 ]  In addition, a combination of computational fluid dynamics and morphological indices have been proposed as reliable predictors of cerebral aneurysm rupture. [ 24 ]


Both high and low wall  shear stress  of flowing blood can cause aneurysm and rupture. However, the mechanism of action is still unknown. It is speculated that low shear stress causes growth and rupture of large aneurysms through inflammatory response while high shear stress causes growth and rupture of small aneurysm through mural response (response from the blood vessel wall). Other risk factors that contributes to the formation of aneurysm are: cigarette smoking, hypertension, female gender, family history of cerebral aneurysm, infection, and trauma. Damage to structural integrity of the arterial wall by shear stress causes an inflammatory response with the recruitment of  T cells ,  macrophages , and  mast cells . The inflammatory mediators are:  interleukin 1 beta ,  interleukin 6 ,  tumor necrosis factor alpha  (TNF alpha),  MMP1 ,  MMP2 ,  MMP9 ,  prostaglandin E2 ,  complement system ,  reactive oxygen species  (ROS), and  angiotensin II . However,  smooth muscle cells  from the  tunica media  layer of the artery moved into the  tunica intima , where the function of the smooth muscle cells changed from contractile function into pro-inflammatory function. This causes the fibrosis of the arterial wall, with reduction of number of smooth muscle cells, abnormal collagen synthesis, resulting in a thinning of the arterial wall and the formation of aneurysm and rupture. No specific gene loci has been identified to be associated with cerebral aneurysms. [ 25 ]


Generally, aneurysms larger than 7 mm in diameter should be treated because they are prone for rupture. Meanwhile, aneurysms less than 7 mm arise from the  anterior  and  posterior communicating artery  and are more easily ruptured when compared to aneurysms arising from other locations. [ 25 ]


Saccular aneurysms are almost always the result of hereditary weaknesses in blood vessels and typically occur within the arteries of the  circle of Willis , [ 20 ] [ 26 ]  in order of frequency affecting the following arteries: [ 27 ]


Saccular aneurysms tend to have a lack of  tunica media  and elastic lamina around their dilated locations (congenital), with a wall of sac made up of thickened hyalinized intima and adventitia. [ 14 ]  In addition, some parts of the brain vasculature are inherently weak—particularly areas along the circle of Willis, where small communicating vessels link the main cerebral vessels. These areas are particularly susceptible to saccular aneurysms. [ 11 ]  Approximately 25% of patients have multiple aneurysms, predominantly when there is a familial pattern. [ 12 ]


Once suspected, intracranial aneurysms can be diagnosed radiologically using  magnetic resonance  or  CT  angiography. [ 28 ]  But these methods have limited sensitivity for diagnosis of small aneurysms, and often cannot be used to specifically distinguish them from infundibular dilations without performing a formal  angiogram . [ 28 ] [ 29 ]  The determination of whether an aneurysm is ruptured is critical to diagnosis.  Lumbar puncture  (LP) is the gold standard technique for determining aneurysm rupture ( subarachnoid hemorrhage ). Once an LP is performed, the  CSF  is evaluated for  RBC count , and presence or absence of  xanthochromia . [ 30 ]


Emergency treatment  for individuals with a ruptured cerebral aneurysm generally includes restoring deteriorating  respiration  and reducing  intracranial pressure . Currently there are two treatment options for securing intracranial aneurysms:  surgical clipping  or  endovascular coiling . If possible, either surgical clipping or endovascular coiling is typically performed within the first 24 hours after bleeding to occlude the ruptured aneurysm and reduce the risk of recurrent hemorrhage. [ 31 ]


While a large  meta-analysis  found the outcomes and risks of surgical clipping and endovascular coiling to be statistically similar, no consensus has been reached. [ 32 ]  In particular, the large  randomised control trial   International Subarachnoid Aneurysm Trial  appears to indicate a higher rate of recurrence when intracerebral aneurysms are treated using endovascular coiling. Analysis of data from this trial has indicated a 7% lower eight-year mortality rate with coiling, [ 33 ]  a high rate of aneurysm recurrence in aneurysms treated with coiling—from 28.6 to 33.6% within a year, [ 34 ] [ 35 ]  a 6.9 times greater rate of late retreatment for coiled aneurysms, [ 36 ]  and a rate of rebleeding 8 times higher than surgically clipped aneurysms. [ 37 ]


Aneurysms can be treated by clipping the base of the aneurysm with a specially-designed clip. Whilst this is typically carried out by  craniotomy , a new endoscopic endonasal approach is being trialled. [ 38 ]  Surgical clipping was introduced by Walter Dandy of the Johns Hopkins Hospital in 1937. [ 39 ]
After clipping, a catheter angiogram or CTA can be performed to confirm complete clipping. [ 40 ]


Endovascular coiling refers to the insertion of  platinum  coils into the aneurysm. A  catheter  is inserted into a blood vessel, typically the  femoral artery , and passed through blood vessels into the cerebral circulation and the aneurysm. Coils are pushed into the aneurysm, or released into the blood stream ahead of the aneurysm. Upon depositing within the aneurysm, the coils expand and initiate a thrombotic reaction within the aneurysm. If successful, this prevents further bleeding from the aneurysm. [ 41 ]  In the case of broad-based aneurysms, a stent may be passed first into the parent artery to serve as a scaffold for the coils. [ 42 ]


Cerebral bypass surgery was developed in the 1960s in Switzerland by  Gazi Yaşargil . When a patient has an aneurysm involving a blood vessel or a tumor at the base of the skull wrapping around a blood vessel, surgeons eliminate the problem vessel by replacing it with an artery from another part of the body. [ 43 ]


Outcomes depend on the size of the aneurysm. [ 44 ]  Small aneurysms (less than 7 mm) have a low risk of rupture and increase in size slowly. [ 44 ]  The risk of rupture is less than one percent for aneurysms of this size. [ 44 ]


The  prognosis  for a ruptured cerebral aneurysm depends on the extent and location of the aneurysm, the person's age, general health, and neurological condition. Some individuals with a ruptured cerebral aneurysm die from the initial bleeding. Other individuals with cerebral aneurysm recover with little or no neurological deficit.  The most significant factors in determining outcome are the  Hunt and Hess grade , and age.  Generally patients with Hunt and Hess grade I and II hemorrhage on admission to the emergency room and patients who are younger within the typical age range of vulnerability can anticipate a good outcome, without death or permanent disability.  Older patients and those with poorer Hunt and Hess grades on admission have a poor prognosis.  Generally, about two-thirds of patients have a poor outcome, death, or permanent disability. [ 20 ] [ 45 ] [ 46 ]