If a certain degree of permanent numbness remains in certain leg muscles, such as the quadriceps, ankles, and feet, this is usually not enough to prevent feeling and sensation, sensing of changes in temperature or pressure, etc. The affected muscle areas simply feel less than before, and the trade-off in ease of movement is said to be immensely worth this change, should it occur.


There is a risk of any of the following more serious risks happening as a result of SDR.


Outcomes following a SDR can vary based on the number of nerves cut during surgery, joint deformities,  muscle contractures , and level of impairment before the procedure. [ 16 ]  Following the procedure, the child will likely experience muscle weakness, which can be corrected with  physical therapy  (PT). PT is imperative to restore functional status in the shortest amount of time. Physical therapy post SDR aims to promote independent walking, improved gait pattern, transfers, balance, and upper limb motor control. It is important to remember SDR does not cause permanent muscle weakness, rather it is temporary a few weeks following the procedure. A strengthening program is beneficial to combat this expected weakness and improve lower extremity range of motion and facilitate a near normal gait pattern. [ 16 ]


This Leeds Children's Hospital website was used as a sample post-rehabilitation protocol. [ 17 ]   Week 1 post surgery, the child will typically have 30 minute physical therapy sessions for the first four days followed by an increase up to 45 minutes during days 5–7. During the second week, sessions range from 45 to 60 minutes with a focus on stretching, strengthening, developmental milestones (if appropriate), and a standing program. If necessary, an orthotic assessment can be performed during the second week. Weeks 3 through 6 focus on the previously mentioned items but adding gait training, assessment for the need of assistive devices, and preparing a home program for the patient. Six weeks to three months following the procedure the patient will attend outpatient physical therapy 3 to 5 times a week for 45–60 minutes and focusing primarily on stretching, strengthening, ambulation, and assessing for the need for adaptive equipment such as a tricycle. Three to six months focus on all previous therapies with emphasis on developing proper gait mechanics. At this point, frequency of the sessions will typically decrease to 2-3 times per week. Six to twelve months post surgery focuses on all of the above with increased emphasis on movement patterns the child may be having difficulty with. One year post procedure, frequency of sessions is 1 to 2 times per week to continue working on strengthening and refining motor control and orthotic needs continued to be monitored. [ 17 ]


A  spinal cord stimulator  ( SCS ) or  dorsal column stimulator  ( DCS ) is a type of implantable  neuromodulation  device (sometimes called a "pain pacemaker") that is used to send electrical signals to select areas of the  spinal cord  (dorsal columns) for the treatment of certain pain conditions. SCS is a consideration for people who have a pain condition that has not responded to more conservative therapy. [ 1 ]  There are also spinal cord stimulators under research and development that could enable patients with  spinal cord injury  to walk again via epidural electrical stimulation (EES). [ 2 ] [ 3 ]


The most common use of SCS is  failed back surgery syndrome  (FBSS) in the United States and peripheral ischemic pain in Europe. [ 4 ] [ 5 ]


As of 2014 the FDA had approved SCS as a treatment for FBSS, chronic pain,  complex regional pain syndrome , intractable angina, as well as visceral abdominal and perineal pain [ 1 ]  and pain in the extremities from nerve damage. [ 6 ]


Once a person has had a  psychological evaluation  and deemed an appropriate candidate for SCS, a temporary implant is placed, called a trial, to determine the best stimulation pattern, and the person is sent home for three to ten days with an external pulse generator.  If pain control and increased activity was achieved, a permanent system, with leads and a pulse generator, is placed. [ 7 ]


SCS may be contraindicated in people who have  coagulation  related disorders, or are on  anticoagulant therapy. [ 1 ]  Other contraindications include local and systemic infection,  pacemakers , or those people for whom pre-surgical imaging studies show have anatomy that makes placement difficult, or if concerns arise during psychological evaluation. [ 8 ] [ 9 ] [ 10 ]


Complications with SCS range from simple easily correctable problems to devastating paralysis, nerve injury and death. In a 7-year follow-up, the overall complication rate was 5–18%. The most common complications include lead migration, lead breakage, and infection. Other complications include rotation of the pulse generator,  haematomas  (subcutaneous or epidural),  cerebrospinal fluid  (CSF) leak,  post dural puncture headache , discomfort at pulse generator site,  seroma  and transient  paraplegia . [ 11 ]


Some people find the tingling sensation caused by older model SCS to be unpleasant.


The most common hardware related complication is lead migration, in which the implanted electrodes move from their original placement. With this complication, recapturing paraesthesia coverage can be attempted with reprogramming. [ 12 ]  In circumstances involving major lead migration a reoperation may be required to reset the lead placement. [ 13 ]  Studies differ greatly in reporting the percentage of people who have lead migration but the majority of studies report in the range of 10-25% of lead migration for spinal cord stimulation. [ 13 ]


The neurophysiological mechanisms of action of spinal cord stimulation are not completely understood but may involve masking pain sensation with  tingling  by altering the pain processing of the  central nervous system . [ 14 ]  The mechanism of analgesia when SCS is applied in  neuropathic  pain states may be very different from that involved in analgesia due to limb ischemia. [ 15 ] [ 16 ]  In neuropathic pain states, experimental evidence shows that SCS alters the local neurochemistry in dorsal horn, suppressing the hyperexcitability of the neurons. Specifically, there is some evidence for increased levels of  GABA  release,  serotonin , and perhaps suppression of levels of some excitatory amino acids, including  glutamate  and  aspartate . In the case of ischemic pain, analgesia seems to derive from restoration of the oxygen demand supply. This effect could be mediated by inhibition of the  sympathetic system , although  vasodilation  is another possibility. It is also probable that a combination of the two above mentioned mechanisms is involved. [ 17 ]


Spinal cord stimulators are placed in two different stages: a trial stage followed by a final implantation stage. First, the skin is prepped and draped utilizing sterile technique. The  epidural space  is accessed with loss of resistance technique using a 14-gauge  Tuohy needle . The lead is fed through carefully with fluoroscopic guidance to the appropriate spinal level. This process is repeated to place another lead adjacent to the first.  Fluoroscopy  is used often during the procedure to identify proper placement of the SCS leads. The lead placement depends on the patient's pain location. Based on previous studies, the lead placement for patients with low back pain is typically T9 to T10. The device technician will then turn on the stimulation, typically starting at a very low frequency. The patient is prompted to describe the sensation perceived by activation of the leads, and the technician will calibrate the SCS to achieve the maximum paresthesia coverage of the patient's targeted pain area. Finally, the leads are anchored externally to reduce risk of lead migration, the site is cleaned, and a clean dressing is applied. Once the patient has recovered from the procedure, the device is once again tested and programmed. [ 18 ]


Patients who are candidates for stimulator placement should be screened for contraindications and comorbidities. The following should be considered prior to stimulator trial: [ 1 ]


In order to assess the efficacy of the spinal cord stimulator before implantation, a trial must be performed. This trial begins with placement of temporary leads into the epidural space and connected percutaneously to an external generator. The trial typically lasts 3–7 days followed by a 2-week reprieve before SCD implantation to ensure that there is no infection from the trial. [ 13 ] [ 20 ]  Successful trial is defined by at least 50% reduction in pain and 80% paresthesia overlap of the original area of pain. If a patient has sudden changes in their pain, then further investigation is needed for possible lead migration or stimulator malfunction. [ 9 ]


Electrotherapy of pain by neurostimulation began shortly after  Melzack  and  Wall  proposed the  gate control theory  in 1965. This theory proposed that nerves carrying painful peripheral stimuli and nerves carrying touch and vibratory sensation both terminate in the  dorsal horn  (the gate) of spinal cord. [ 21 ]  It was hypothesized that input to the latter could be manipulated to "close the gate" to the former. As an application of the gate control theory, Shealy et al. [ 22 ]  implanted the first spinal cord stimulator device directly on the dorsal column for the treatment of chronic pain and in 1971, Shimogi and colleagues first reported the analgesic properties of epidural spinal cord stimulation. Since then this technique has undergone numerous technical and clinical developments.


At this time neurostimulation for the treatment of pain is used with  nerve  stimulation, spinal cord stimulation,  deep brain stimulation , and  motor cortex  stimulation.


SCS has been studied in people with Parkinson's disease [ 23 ]  and  angina pectoris . [ 24 ]


Research on improving the devices and software has included efforts to increasing the battery life, efforts to develop  closed loop  control, and combining stimulation with implanted drug delivery systems. [ 23 ]


SCS is being studied to treat spinal cord injury. In August 2018, The European Commission's Horizon 2020  Future and Emerging Technologies  program announced a $3.5 million funding grant for the four-nation project team that is building a prototype of an implant designed to 'rewire' the spinal cord. [ 25 ]  In September 2018,  Mayo Clinic  and  UCLA  reported that spinal cord stimulation supported with physical therapy can help people with paralysis to regain their ability to stand and walk with assistance. [ 26 ]  In December 2019, the first double blinded, randomized controlled pivotal study in the history of spinal cord stimulation was published in  Lancet Neurology . [ 27 ]


Stereotactic surgery  is a  minimally invasive  form of  surgical  intervention that makes use of a three-dimensional  coordinate  system to locate small targets inside the body and to perform on them some action such as  ablation ,  biopsy ,  lesion , injection,  stimulation , implantation,  radiosurgery  (SRS), etc.


In theory, any organ system inside the body can be subjected to stereotactic surgery. However, difficulties in setting up a reliable frame of reference (such as  bone  landmarks, which bear a constant spatial relation to soft tissues) mean that its applications have been, traditionally and until recently, limited to  brain surgery . Besides the  brain , biopsy and surgery of the  breast  are done routinely to locate, sample (biopsy), and remove tissue. Plain X-ray images ( radiographic  mammography),  computed tomography , and  magnetic resonance imaging  can be used to  guide  the procedure.


Another accepted form of "stereotactic" is "stereotaxic". The  word roots  are  stereo- , a prefix derived from the  Greek  word στερεός ( stereos , "solid"), and  -taxis  (a suffix of  Neo-Latin  and  ISV , derived from Greek  taxis , "arrangement", "order", from  tassein , "to arrange").


The surgery is used to treat various brain cancers, benign, and functional disorders of the brain. [ 1 ]  This is sometimes combined with  whole brain radiotherapy , and a 2021 systematic review found  this combination led to the greatest improvement of survival for those with single brain metastasis. [ 2 ]


Amongst the malignant brain disorders are: brain metastasis and  glioblastoma . [ 1 ]  The benign brain disorders are:  meningioma ,  cerebral arteriovenous malformation ,  vestibular schwannoma , and  pituitary adenoma . [ 1 ]  Functional disorders are:  trigeminal neuralgia ,  Parkinson's disease , and  epilepsy . [ 1 ]


Stereotactic surgery works on the basis of three main components: [ citation needed ]


Modern stereotactic planning systems are computer based. The stereotactic atlas is a series of cross sections of anatomical structure (for example, a human brain), depicted in reference to a two-coordinate frame. Thus, each brain structure can be easily assigned a range of three coordinate numbers, which will be used for positioning the stereotactic device. In most atlases, the three dimensions are: latero-lateral ( x ), dorso-ventral ( y ) and rostro-caudal ( z ).


The stereotactic apparatus uses a set of three coordinates ( x ,  y  and  z ) in an orthogonal frame of reference ( cartesian coordinates ), or, alternatively, a  cylindrical coordinates  system, also with three coordinates: angle, depth and antero-posterior (or axial) location. The mechanical device has head-holding clamps and bars which puts the head in a fixed position in reference to the coordinate system (the so-called zero or origin). In small laboratory animals, these are usually  bone  landmarks which are known to bear a constant spatial relation to soft tissue. For example, brain atlases often use the  external auditory meatus , the inferior  orbital  ridges, the median point of the  maxilla  between the  incisive teeth . or the  bregma  (confluence of sutures of frontal and parietal bones), as such landmarks. In humans, the reference points, as described above, are intracerebral structures which are clearly discernible in a  radiograph  or  tomograph . In newborn human babies, the "soft spot" where the coronal and sagittal sutures meet (known as the  fontanelle ) becomes the bregma when this gap closes. [ 3 ]


Guide bars in the  x ,  y  and  z  directions (or alternatively, in the polar coordinate holder), fitted with high precision  vernier scales  allow the neurosurgeon to position the point of a probe (an  electrode , a  cannula , etc.) inside the brain, at the calculated coordinates for the desired structure, through a small trephined hole in the skull.


Currently, a number of manufacturers produce stereotactic devices fitted for  neurosurgery  in humans, for both brain and spine procedures, as well as for animal experimentation.


Stereotactic radiosurgery utilizes externally generated  ionizing radiation  to inactivate or eradicate defined targets in the head or spine without the need to make an incision. [ 5 ]  This concept requires steep dose gradients to reduce injury to adjacent normal tissue while maintaining treatment efficacy in the target. [ 6 ]  As a consequence of this definition, the overall treatment accuracy should match the treatment planning margins of 1–2  mm  or better. [ 7 ]  To use this paradigm optimally and treat patients with the highest possible  accuracy and precision , all errors, from image acquisition over treatment planning to mechanical aspects of the delivery of treatment and intra-fraction motion concerns, must be systematically optimized. [ 8 ]  To assure quality of patient care the procedure involves a multidisciplinary team consisting of a  radiation oncologist ,  medical physicist , and radiation therapist. [ 9 ] [ 10 ]  Dedicated, commercially available stereotactic radiosurgery programs are provided by the irrespective  Gamma Knife , [ 11 ]   CyberKnife , [ 12 ]  and Novalis Radiosurgery [ 13 ]  devices. [ 14 ]


Stereotactic radiosurgery provides an efficient, safe, and minimal invasive treatment alternative [ 15 ]  for patients diagnosed with  malignant ,  benign  and  functional indications  in the brain and spine, including but not limited to both  primary  and  secondary tumors . [ 16 ]  Stereotactic radiosurgery is a well-described management option for most  metastases ,  meningiomas ,  schwannomas ,  pituitary adenomas ,  arteriovenous malformations , and  trigeminal neuralgia , among others. [ 17 ]


Irrespective of the similarities between the concepts of stereotactic radiosurgery and fractionated  radiotherapy  and although both treatment modalities are reported to have identical outcomes for certain indications, [ 18 ]  the intent of both approaches is fundamentally different. The aim of stereotactic radiosurgery is to destroy target tissue while preserving adjacent normal tissue, where fractionated radiotherapy relies on a different sensitivity of the target and the surrounding normal tissue to the total accumulated radiation  dose . [ 5 ]  Historically, the field of fractionated radiotherapy evolved from the original concept of stereotactic radiosurgery following discovery of the principles of  radiobiology : repair, reassortment, repopulation, and reoxygenation. [ 19 ]  Today, both treatment techniques are complementary as tumors that may be resistant to fractionated radiotherapy may respond well to radiosurgery and tumors that are too large or too close to critical organs for safe radiosurgery may be suitable candidates for fractionated radiotherapy. [ 18 ]


A second, more recent evolution extrapolates the original concept of stereotactic radiosurgery to extra-cranial targets, most notably in the lung, liver, pancreas, and prostate. This treatment approach, entitled stereotactic body radiotherapy or SBRT, is challenged by various types of motion. [ 20 ]  On top of patient immobilization challenges and the associated patient motion, extra-cranial lesions move with respect to the patient's position due to respiration, bladder and rectum filling. [ 21 ]  Like stereotactic radiosurgery, the intent of stereotactic body radiotherapy is to eradicate a defined extra-cranial target. However, target motion requires larger treatment margins around the target to compensate for the positioning uncertainty. This in turn implies more normal tissue exposed to high doses, which could result in negative treatment  side effects . As a consequence, stereotactic body radiotherapy is mostly delivered in a limited number of fractions, thereby blending the concept of stereotactic radiosurgery with the therapeutic benefits of fractionated radiotherapy. [ 22 ]  To monitor and correct target motion for accurate and precise patient positioning prior and during treatment, advanced  image-guided technologies  are commercially available and included in the radiosurgery programs offered by the CyberKnife and Novalis communities. [ 23 ]


Functional neurosurgery comprises treatment of several disorders such as  Parkinson's disease ,  hyperkinesia , disorder of muscle tone, intractable pain, convulsive disorders and psychological phenomena. Treatment for these phenomena was believed to be located in the superficial parts of the CNS and PNS. Most of the interventions made for treatment consisted of cortical extirpation.
To alleviate extra pyramidal disorders, pioneer Russell Meyers dissected or transected the head of the  caudate nucleus  in 1939, [ 24 ]  and part of the  putamen  and  globus pallidus .
Attempts to abolish intractable pain were made with success by transection of the  spinothalamic tract  at spinal medullary level and further proximally, even at mesencephalic levels. [ citation needed ]


In 1939-1941 Putnam and Oliver tried to improve Parkinsonism and hyperkinesias by trying a series of modifications of the lateral and antero-lateral  cordotomies . Additionally, other scientists like Schurman, Walker, and Guiot made significant contributions to functional neurosurgery. In 1953, Cooper discovered by chance that ligation of the anterior chorioidal artery resulted in improvement of Parkinson's disease. Similarly, when Grood was performing an operation in a patient with Parkinson's, he accidentally lesioned the  thalamus . This caused the patient's tremors to stop. From then on, thalamic lesions became the target point with more satisfactory results. [ 25 ]


More recent clinical applications can be seen [ 26 ]  in surgeries used to treat Parkinson's disease, such as  Pallidotomy  or  Thalamotomy  (lesioning procedures), or  Deep Brain Stimulation  (DBS). [ 27 ]  During DBS, an electrode is placed into the thalamus, the pallidum of the subthalmamic nucleus, parts of brain that are involved in motor control, and are affected by Parkinson's disease. The electrode is connected to a small battery operated stimulator that is placed under the collarbone, where a wire runs beneath the skin to connect it to the electrode in the brain. The stimulator produces electrical impulses that affect the nerve cells around the electrode and should help alleviate tremors or symptoms that are associated with the affected area. [ citation needed ]


In  Thalamotomy , a needle electrode is placed into the thalamus, and the patient must cooperate with tasks assigned to find the affected area- after this area of the thalamus is located, a small high frequency current is applied to the electrode and this destroys a small part of the thalamus. Approximately 90% of patients experience instantaneous tremor relief. [ citation needed ]


In  Pallidotomy , an almost identical procedure to thalamotomy, a small part of the pallidum is destroyed and 80% of patients see improvement in rigidity and hypokinesia and a tremor relief or improvement comes weeks after the procedure. [ citation needed ]


The stereotactic method was first published in 1908 by two British scientists,  Victor Horsley , a physician and neurosurgeon, and Robert H. Clarke, a physiologist and was built by Swift & Son; the two scientists stopped collaborating after the 1908 publication.  The Horsley–Clarke apparatus used a  Cartesian  (three-orthogonal axis) system.  That device is in the  Science Museum, London ; a copy was brought to the US by  Ernest Sachs  and is in the Department of Neurosurgery at  UCLA .  Clarke used the original to do research that led to publications of primate and cat  brain atlases .  There is no evidence it was ever used in a human surgery. [ 28 ] [ 29 ] : 12  [ 30 ]   The first stereotactic device designed for the human brain appears to have been an adaptation of the Horseley–Clarke frame built at Aubrey T. Mussen's behest by a London workshop in 1918, but it received little attention and does not appear to have been used on people.  It was a frame made of brass. [ 29 ] : 12  [ 31 ]


The first stereotactic device used in humans was used by  Martin Kirschner , for a method to treat  trigeminal neuralgia  by inserting an electrode into the trigeminal nerve and ablating it.  He published this in 1933. [ 29 ] : 13  [ 32 ] : 420  [ 33 ]


In 1947 and 1949, two neurosurgeons working at Temple University in Philadelphia, Ernest A. Spiegel (who had fled Austria when the Nazis took over [ 28 ] ) and Henry T. Wycis, published their work on a device similar to the Horsley–Clarke apparatus in using a cartesian system; it was attached to the patient's head with a plaster cast instead of screws.  Their device was the first to be used for brain surgery; they used it for  psychosurgery .  They also created the first atlas of the human brain, and used intracranial reference points, generated by using medical images acquired with contrast agents. [ 29 ] : 13  [ 32 ] : 72  [ 34 ]


The work of Spiegel and Wycis sparked enormous interest and research. [ 29 ] : 13   In Paris,  Jean Talairach  collaborated with Marcel David, Henri Hacaen, and  Julian de Ajuriaguerra  on a stereotactic device, publishing their first work in 1949 and eventually developing the  Talairach coordinates . [ 28 ] [ 29 ] : 13  [ 32 ] : 93    In Japan,  Hirotaro Narabayashi  was doing similar work. [ 28 ]


In 1949,  Lars Leksell  published a device that used  polar coordinates  instead of cartesian, and two years later he published work where he used his device to target a beam of radiation into a brain. [ 29 ] : 13  [ 32 ] : 91  [ 35 ] [ 36 ]   Leksell's radiosurgery system is also used by the  Gamma Knife  device, and by other neurosurgeons, using  linear accelerators , proton beam therapy and neutron capture therapy. Lars Leksell went on to commercialize his inventions by founding  Elekta  in 1972. [ 37 ]


In 1979,  Russell A. Brown  proposed a device, [ 38 ]  now known as the  N-localizer , [ 39 ]  that enables guidance of stereotactic surgery using tomographic images that are obtained via medical imaging technologies such as  X-ray computed tomography  (CT), [ 40 ]   magnetic resonance imaging  (MRI), [ 41 ]  or  positron emission tomography  (PET). [ 42 ]  The N-localizer comprises a diagonal rod that spans two vertical rods to form an N-shape that allows tomographic images to be mapped to physical space. [ 43 ]  This device became almost universally adopted by the 1980s [ 44 ]  and is included in the Brown-Roberts-Wells (BRW), [ 45 ]  Kelly-Goerss, [ 46 ]  Leksell, [ 47 ]  Cosman-Roberts-Wells (CRW), [ 48 ]  Micromar-ETM03B, FiMe-BlueFrame, Macom, and Adeor-Zeppelin [ 49 ]  stereotactic frames and in the Gamma Knife  radiosurgery  system. [ 44 ]  An alternative to the N-localizer is the Sturm-Pastyr localizer [ 50 ]  that is included in the Riechert-Mundinger and Zamorano-Dujovny stereotactic frames. [ 51 ]


Other localization methods also exist that do not make use of tomographic images produced by CT, MRI, or PET, but instead conventional radiographs. [ 52 ]


The stereotactic method has continued to evolve, and at present employs an elaborate mixture of  image-guided surgery  that uses  computed tomography ,  magnetic resonance imaging  and stereotactic localization. [ citation needed ]


In 1970, in the city of Buenos Aires, Argentina, Aparatos Especiales company, produced the first Stereotactic System in Latin America. Antonio Martos Calvo, together with Jorge Candia and Jorge Olivetti through the request of neurosurgeon Jorge Schvarc (1942-2019), developed an equipment based on the principle of Hitchcock Stereotactic System. The patient was seated in an adapted chair with two telescopic arms attached at it base, which fixed the stereotactic frame preventing the patient’s movement.


A double radiopaque ruler attached to the side of the frame made it possible to obtain the antero-posterior and latero-lateral X-ray images without the need of moving the radiopaque ruler. The thermal coagulation lesion was performed using tungsten monopole electrodes of 1,5mm of diameter (without temperature control) with a 3mm active tip, utilizing an electrical bipolar coagulator. The lesion size was previously determined by testing the electrode in egg albumin. Coagulation size was the result of the electrical coagulator power regulation and the application time of the radiofrequency. The first surgery performed with this system was a Trigeminal Nucleotractothomy. Jorge Schvarcz performed more than 700 functional surgeries until 1994 when, due to health problems he stopped exercising his profession. But the equipment developed kept improving on a neurosurgery history.


This was the beginning of the developing of technology to produce stereotactic devices in Latin America. This was the beginning of the first stereotactic manufacturer of Latin America – The Brazilian Micromar.


Stereotactic surgery is sometimes used to aid in several different types of animal research studies.  Specifically, it is used to target specific sites of the brain and directly introduce pharmacological agents to the brain which otherwise may not be able to cross the  blood–brain barrier . [ 53 ]   In rodents, the main applications of stereotactic surgery are to introduce fluids directly to the brain or to implant  cannulae  and  microdialysis  probes. Site specific central microinjections are used when rodents do not need to be awake and behaving or when the substance to be injected has a long duration of action.  For protocols in which rodents’ behaviors must be assessed soon after injection, stereotactic surgery can be used to implant a cannula through which the animal can be injected after recovery from the surgery.  These protocols take longer than site-specific central injections in anesthetized mice because they require the construction of cannulae, wire plugs, and injection needles, but induce less stress in the animals because they allow for a recovery period for the healing of trauma induced to the brain before injection. [ 54 ]   Surgery can also be used for microdialysis protocols to implant and tether the dialysis probe and guide cannula. [ 55 ]


A  stereotaxic atlas  is a number of records of brain structure of a particular animal accompanied with coordinates used in  stereotactic surgery . Stereotaxic atlases are developed using MRI data from a large number of subjects to visualize the topology of the brain. [ 1 ]  This allows for highly accurate, minimally invasive surgery based on 3D imaging. The development of stereotaxic atlases has been particularly important in making it possible to operate on areas deep in the brain that are not accessible through traditional surgical methods. [ 2 ]


Subarachnoid hemorrhage  ( SAH ) is  bleeding  into the  subarachnoid space —the area between the  arachnoid membrane  and the  pia mater  surrounding the  brain . [ 1 ]  Symptoms may include a  severe headache of rapid onset , vomiting,  decreased level of consciousness ,  fever , weakness, numbness, and sometimes  seizures . [ 1 ]  Neck stiffness or neck pain are also relatively common. [ 2 ]  In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed. [ 1 ]


SAH may occur as a result of a  head injury  or spontaneously, usually from a ruptured  cerebral aneurysm . [ 1 ]  Risk factors for spontaneous cases include  high blood pressure , smoking, family history, alcoholism, and  cocaine  use. [ 1 ]  Generally, the diagnosis can be determined by a  CT scan  of the head if done within six hours of symptom onset. [ 2 ]  Occasionally, a  lumbar puncture  is also required. [ 2 ]  After confirmation further tests are usually performed to determine the underlying cause. [ 2 ]


Treatment is by prompt  neurosurgery  or  endovascular coiling . [ 1 ]  Medications such as  labetalol  may be required to lower the blood pressure until repair can occur. [ 1 ]  Efforts to treat fevers are also recommended. [ 1 ]   Nimodipine , a  calcium channel blocker , is frequently used to prevent  vasospasm . [ 1 ]  The routine use of medications to prevent further seizures is of unclear benefit. [ 1 ]  Nearly half of people with a SAH due to an underlying aneurysm die within 30 days and about a third who survive have ongoing problems. [ 1 ]  Between ten and fifteen percent die before reaching a hospital. [ 4 ]


Spontaneous SAH occurs in about one per 10,000 people per year. [ 1 ]  Females are more commonly affected than males. [ 1 ]  While it becomes more common with age, about 50% of people present under 55 years old. [ 4 ]  It is a form of  stroke  and comprises about 5 percent of all strokes. [ 4 ]  Surgery for aneurysms was introduced in the 1930s. [ 5 ]  Since the 1990s many aneurysms are treated by a less invasive procedure called  endovascular coiling , which is carried out through a large blood vessel. [ 6 ]


A true subarachnoid hemorrhage may be confused with a  pseudosubarachnoid hemorrhage , an apparent increased  attenuation  on  CT scans  within the  basal cisterns  that mimics a true subarachnoid hemorrhage. [ 7 ]  This occurs in cases of severe  cerebral edema , such as by  cerebral hypoxia . It may also occur due to  intrathecally administered   contrast material , [ 8 ]  leakage of high-dose  intravenous  contrast material into the  subarachnoid spaces , or in patients with  cerebral venous sinus thrombosis , severe  meningitis ,  leptomeningeal carcinomatosis , [ 9 ]   intracranial hypotension ,  cerebellar infarctions , or  bilateral   subdural hematomas . [ 10 ]


The classic symptom of subarachnoid hemorrhage is  thunderclap headache  (a headache described as "like being kicked in the head", [ 3 ]  or the "worst ever", developing over seconds to minutes). This headache often pulsates towards the  occiput  (the back of the head). [ 11 ]  About one-third of people have no symptoms apart from the characteristic headache, and about one in ten people who seek medical care with this symptom are later diagnosed with a subarachnoid hemorrhage. [ 4 ]  Vomiting may be present, and 1 in 14 have  seizures . [ 4 ]   Confusion , decreased level of consciousness or  coma  may be present, as may neck stiffness and other signs of  meningism . [ 4 ]


Neck stiffness usually presents six hours after initial onset of SAH. [ 12 ]  Isolated  dilation  of a pupil and loss of the  pupillary light reflex  may reflect  brain herniation  as a result of rising  intracranial pressure  (pressure inside the skull). [ 4 ]   Intraocular hemorrhage  (bleeding into the eyeball) may occur in response to the raised pressure: subhyaloid hemorrhage (bleeding under the  hyaloid membrane , which envelops the  vitreous body  of the eye) and vitreous hemorrhage may be visible on  fundoscopy . This is known as  Terson syndrome  (occurring in 3–13 percent of cases) and is more common in more severe SAH. [ 13 ]


Oculomotor nerve  abnormalities (affected eye looking downward and outward and  inability to lift the eyelid on the same side ) or  palsy  (loss of movement) may indicate bleeding from the  posterior communicating artery . [ 4 ] [ 11 ]  Seizures are more common if the hemorrhage is from an aneurysm; it is otherwise difficult to predict the site and origin of the hemorrhage from the symptoms. [ 4 ]  SAH in a person known to have seizures is often diagnostic of a  cerebral arteriovenous malformation . [ 11 ]


The combination of intracerebral hemorrhage and raised intracranial pressure (if present) leads to a "sympathetic surge", i.e. over-activation of the sympathetic system. This is thought to occur through two mechanisms, a direct effect on the  medulla  that leads to activation of the descending  sympathetic nervous system  and a local release of inflammatory mediators that circulate to the peripheral circulation where they activate the sympathetic system. As a consequence of the sympathetic surge there is a sudden increase in  blood pressure ; mediated by increased  contractility  of the  ventricle  and increased  vasoconstriction  leading to increased  systemic vascular resistance . The consequences of this sympathetic surge can be sudden, severe, and are frequently life-threatening. The high  plasma  concentrations of adrenaline also may cause  cardiac arrhythmias  (irregularities in the heart rate and rhythm),  electrocardiographic changes  (in 27 percent of cases) [ 14 ]  and  cardiac arrest  (in 3 percent of cases) may occur rapidly after the onset of hemorrhage. [ 4 ] [ 15 ]  A further consequence of this process is  neurogenic   pulmonary edema , [ 16 ]  where a process of increased pressure within the pulmonary circulation causes leaking of fluid from the pulmonary  capillaries  into the air spaces, the  alveoli , of the lung. [ 17 ] [ 18 ]


Subarachnoid hemorrhage may also occur in people who have had a head injury. Symptoms may include headache, decreased level of consciousness and  hemiparesis  (weakness of one side of the body). SAH is a frequent occurrence in traumatic brain injury and carries a poor prognosis if it is associated with deterioration in the level of consciousness. [ 19 ]


While thunderclap headache is the characteristic symptom of subarachnoid hemorrhage, less than 10% of those with concerning symptoms have SAH on investigations. [ 2 ]  A number of other causes may need to be considered. [ 20 ]


Most cases of SAH are due to  trauma  such as a blow to the head. [ 1 ] [ 21 ]  Traumatic SAH usually occurs near the site of a  skull fracture  or  intracerebral contusion . [ 22 ]  It often happens in the setting of other forms of traumatic brain injury. In these cases prognosis is poorer; however, it is unclear if this is a direct result of the SAH or whether the presence of subarachnoid blood is simply an indicator of a more severe head injury. [ 23 ]


In 85 percent of spontaneous cases the cause is a  cerebral aneurysm —a weakness in the wall of one of the  arteries  in the brain that becomes enlarged. They tend to be located in the  circle of Willis  and its branches. While most cases are due to bleeding from small aneurysms, larger aneurysms (which are less common) are more likely to rupture. [ 4 ]   Aspirin  also appears to increase the risk. [ 24 ]


In 15–20 percent of cases of spontaneous SAH, no aneurysm is detected on the first  angiogram . [ 22 ]  About half of these are attributed to non-aneurysmal perimesencephalic hemorrhage, in which the blood is limited to the subarachnoid spaces around the  midbrain  (i.e. mesencephalon). In these, the origin of the blood is uncertain. [ 4 ]  The remainder are due to other disorders affecting the blood vessels (such as  cerebral arteriovenous malformations ), disorders of the blood vessels in the  spinal cord , and bleeding into various  tumors . [ 4 ]


Cocaine  abuse and  sickle cell anemia  (usually in children) and, rarely,  anticoagulant  therapy,  problems with blood clotting  and  pituitary apoplexy  can also result in SAH. [ 12 ] [ 22 ]   Dissection of the vertebral artery , usually caused by trauma, can lead to subarachnoid hemorrhage if the dissection involves the part of the vessel inside the skull. [ 25 ]


Cerebral vasospasm is one of the complications caused by subarachnoid hemorrhage. It usually happens from the third day after the aneurysm event, and reaches its peak on 5th to 7th day. [ 26 ]  There are several mechanisms proposed for this complication. Blood products released from subarachnoid hemorrhage stimulates the  tyrosine kinase  pathway causing the release of calcium ions from intracellular storage, resulting in smooth muscle contraction of cerebral arteries.  Oxyhaemoglobin  in  cerebrospinal fluid  (CSF) causes vasoconstriction by increasing  free radicals ,  endothelin-1 ,  prostaglandin  and reducing the level of  nitric oxide  and  prostacyclin . Besides, the disturbances of  autonomic nervous system  innervating cerebral arteries is also thought to cause vasospasm. [ 27 ]


As only 10 percent of people admitted to the emergency department with a thunderclap headache are having an SAH, other possible causes are usually considered simultaneously, such as  meningitis ,  migraine , and  cerebral venous sinus thrombosis . [ 3 ]   Intracerebral hemorrhage , in which bleeding occurs within the brain itself, is twice as common as SAH and is often misdiagnosed as the latter. [ 28 ]  It is not unusual for SAH to be initially misdiagnosed as a migraine or  tension headache , which can lead to a delay in obtaining a CT scan. In a 2004 study, this occurred in 12 percent of all cases and was more likely in people who had smaller hemorrhages and no impairment in their mental status. The delay in diagnosis led to a worse outcome. [ 29 ]  In some people, the headache resolves by itself, and no other symptoms are present. This type of headache is referred to as "sentinel headache", because it is presumed to result from a small leak (a "warning leak") from an aneurysm. A sentinel headache still warrants investigations with CT scan and lumbar puncture, as further bleeding may occur in the subsequent three weeks. [ 30 ]


The initial steps for evaluating a person with a suspected subarachnoid hemorrhage are obtaining a  medical history  and performing a  physical examination . The diagnosis cannot be made on clinical grounds alone and in general  medical imaging  and possibly a lumbar puncture is required to confirm or exclude bleeding. [ 2 ]


The modality of choice is  computed tomography  (CT scan), without  contrast , of the brain. This has a high  sensitivity  and will correctly identify 98.7% of cases within six hours of the onset of symptoms. [ 31 ]  A CT scan can rule out the diagnosis in someone with a normal neurological exam if done within six hours. [ 32 ]  Its efficacy declines thereafter, [ 1 ]  and  magnetic resonance imaging  (MRI) is more sensitive than CT after several days. [ 4 ]


After a subarachnoid hemorrhage is confirmed, its origin needs to be determined. If the bleeding is likely to have originated from an aneurysm (as determined by the CT scan appearance), the choice is between  cerebral angiography  (injecting radiocontrast through a  catheter  to the brain arteries) and  CT angiography  (visualizing  blood vessels  with  radiocontrast  on a CT scan) to identify aneurysms. Catheter angiography also offers the possibility of coiling an aneurysm (see below). [ 4 ] [ 30 ]


In emergency department patients complaining of acute-onset headache without significant risk factors for SAH, evidence suggests that CT scanning of the head followed by CT angiography can reliably exclude SAH without the need for a lumbar puncture. [ 33 ]  The risk of missing an aneurysmal bleed as the cause of SAH with this approach is less than 1%. [ 33 ]


Lumbar puncture , in which  cerebrospinal fluid  (CSF) is removed from the  subarachnoid space  of the  spinal canal  using a  hypodermic needle , shows evidence of bleeding in three percent of people in whom a non-contrast CT was found normal. [ 4 ]  A lumbar puncture or CT scan with contrast is therefore regarded as mandatory in people with suspected SAH when imaging is delayed to after six hours from the onset of symptoms and is negative. [ 4 ] [ 32 ]  At least three tubes of CSF are collected. [ 12 ]  If an elevated number of  red blood cells  is present equally in all bottles, this indicates a subarachnoid hemorrhage. If the number of cells decreases per bottle, it is more likely that it is due to damage to a small blood vessel during the procedure (known as a "traumatic tap"). [ 30 ]  While there is no official cutoff for red blood cells in the CSF no documented cases have occurred at less than "a few hundred cells" per high-powered field. [ 34 ]


The CSF sample is also examined for  xanthochromia —the yellow appearance of  centrifugated  fluid. This can be determined by  spectrophotometry  (measuring the absorption of particular wavelengths of light) or visual examination. It is unclear which method is superior. [ 35 ]  Xanthochromia remains a reliable ways to detect SAH several days after the onset of headache. [ 36 ]  An interval of at least 12 hours between the onset of the headache and lumbar puncture is required, as it takes several hours for the hemoglobin from the red blood cells to be metabolized into  bilirubin . [ 4 ] [ 36 ]


Electrocardiographic  changes are relatively common in subarachnoid hemorrhage, occurring in 40–70 percent of cases. They may include  QT prolongation ,  Q waves ,  cardiac dysrhythmias , and  ST elevation  that mimics a  heart attack . [ 37 ]


Also one of the characteristic  ECG  changes that could be found in patients with subarachnoid hemorrhage, is the  J waves  or Osborn waves, which are positive deflections that occur at the junction between  QRS complexes  and  ST segments , where the S point, also known as the J point, has a myocardial infarction-like elevation. [ 38 ]  J waves or Osborn waves, which represent an early  repolarization  and delayed  depolarization  of the heart ventricles, are thought to be caused by the high  catecholamines  surge released in patients with subarachnoid hemorrhage or brain damage, the issue that might lead to  ventricular fibrillation  and  cardiac arrest  in unmanaged patients. [ 39 ] [ 40 ]


There are several grading scales available for SAH. The  Glasgow Coma Scale  (GCS) is ubiquitously used for assessing consciousness. Its three specialized scores are used to evaluate SAH; in each, a higher number is associated with a worse outcome. [ 41 ]  These scales have been derived by retrospectively matching characteristics of people with their outcomes.


The first widely used scale for neurological condition following SAH was published by  Botterell  and Cannell in 1956 and referred to as the Botterell Grading Scale. This was modified by Hunt and Hess [ 42 ] [ 43 ] [ 44 ]  in 1968: [ 45 ]


The Fisher Grade classifies the appearance of subarachnoid hemorrhage on CT scan. [ 46 ]


This scale has been modified by Claassen and coworkers, reflecting the additive risk from SAH size and accompanying  intraventricular hemorrhage  (0 – none; 1 – minimal SAH w/o IVH; 2 – minimal SAH with IVH; 3 – thick SAH w/o IVH; 4 – thick SAH with IVH);. [ 47 ]


The World Federation of Neurosurgeons (WFNS) classification uses Glasgow coma score and  focal neurological deficit  to gauge severity of symptoms. [ 48 ]


A comprehensive  classification scheme  has been suggested by Ogilvy and Carter to predict outcome and gauge therapy. [ 49 ]  The system consists of five grades and it assigns one point for the presence or absence of each of five factors: age greater than 50; Hunt and Hess grade 4 or 5; Fisher scale 3 or 4; aneurysm size greater than 10 mm; and posterior circulation aneurysm 25 mm or more. [ 49 ]


Screening  for aneurysms is not performed on a population level; because they are relatively rare, it would not be  cost-effective . However, if someone has two or more first-degree relatives who have had an aneurysmal subarachnoid hemorrhage, screening may be worthwhile. [ 4 ] [ 50 ]


Autosomal dominant polycystic kidney disease  (ADPKD), a hereditary kidney condition, is known to be associated with cerebral aneurysms in 8 percent of cases, but most such aneurysms are small and therefore unlikely to rupture. As a result, screening is only recommended in families with ADPKD where one family member has had a ruptured aneurysm. [ 51 ]


An aneurysm may be detected incidentally on brain imaging; this presents a conundrum, as all treatments for cerebral aneurysms are associated with potential complications. The International Study of Unruptured Intracranial Aneurysms (ISUIA) provided prognostic data both in people having previously had a subarachnoid hemorrhage and people who had aneurysms detected by other means. Those having previously had a SAH were more likely to bleed from other aneurysms. In contrast, those having never bled and had small aneurysms (smaller than 10 mm) were very unlikely to have a SAH and were likely to sustain harm from attempts to repair these aneurysms. [ 52 ]  On the basis of the ISUIA and other studies, it is now recommended that people are considered for  preventive treatment  only if they have a reasonable  life expectancy  and have aneurysms that are highly likely to rupture. [ 50 ]  Moreover, there is only limited evidence that endovascular treatment of unruptured aneurysms is actually beneficial. [ 53 ]


Management involves general measures to stabilize the person while also using specific investigations and treatments. These include the prevention of rebleeding by obliterating the bleeding source, prevention of a phenomenon known as  vasospasm , and prevention and treatment of complications. [ 4 ]


Stabilizing the person is the first priority. Those with a depressed level of consciousness may need to be  intubated  and  mechanically ventilated . Blood pressure,  pulse ,  respiratory rate , and Glasgow Coma Scale are monitored frequently. Once the diagnosis is confirmed, admission to an  intensive care unit  may be preferable, especially since 15 percent may have further bleeding soon after admission. Nutrition is an early priority, mouth or  nasogastric tube  feeding being preferable over  parenteral  routes. In general, pain control is restricted to less-sedating agents such as  codeine , as  sedation  may impact on the mental status and thus interfere with the ability to monitor the level of consciousness.  Deep vein thrombosis  is prevented with  compression stockings , intermittent  pneumatic  compression of the  calves , or both. [ 4 ]  A  bladder catheter  is usually inserted to monitor fluid balance.  Benzodiazepines  may be administered to help relieve distress. [ 12 ]   Antiemetic  drugs should be given to awake persons. [ 11 ]


People with poor clinical grade on admission, acute neurologic deterioration, or progressive enlargement of ventricles on CT scan are, in general, indications for the placement of an  external ventricular drain  by a neurosurgeon. The external ventricular drain may be inserted at the bedside or in the operating room. In either case, strict  aseptic technique  must be maintained during insertion. In people with aneurysmal subarachnoid hemorrhage the EVD is used to remove  cerebrospinal fluid , blood, and blood byproducts that increase  intracranial pressure  and may increase the risk for  cerebral vasospasm . [ 54 ]


Efforts to keep a person's  systolic blood pressure  somewhere between 140 and 160 mmHg is generally recommended. [ 1 ]  Medications to achieve this may include  labetalol  or  nicardipine . [ 1 ]


People whose CT scan shows a large  hematoma , depressed level of consciousness, or  focal neurologic signs  may benefit from urgent surgical removal of the blood or occlusion of the bleeding site. The remainder are stabilized more extensively and undergo a  transfemoral angiogram  or CT angiogram later. It is hard to predict who will have a rebleed, yet it may happen at any time and carries a dismal prognosis. After the first 24 hours have passed, rebleeding risk remains around 40 percent over the subsequent four weeks, suggesting that interventions should be aimed at reducing this risk as soon as possible. [ 4 ]  Some predictors of early rebleeding are high systolic blood pressure, the presence of a hematoma in the brain or ventricles, poor Hunt-Hess grade (III-IV), aneurysms in the posterior circulation, and an aneurysm >10 mm in size. [ 55 ]


If a  cerebral aneurysm  is identified on angiography, two measures are available to reduce the risk of further bleeding from the same aneurysm:  clipping [ 56 ]  and  coiling . [ 57 ]  Clipping requires a  craniotomy  (opening of the skull) to locate the aneurysm, followed by the placement of clips around the neck of the aneurysm. Coiling is performed through the large blood vessels (endovascularly): a catheter is inserted into the  femoral artery  in the groin and advanced through the  aorta  to the arteries (both  carotid arteries  and both  vertebral arteries ) that supply the brain. When the aneurysm has been located,  platinum  coils are deployed that cause a  blood clot to form  in the aneurysm, obliterating it. The decision as to which treatment is undertaken is typically made by a multidisciplinary team consisting of a  neurosurgeon ,  neuroradiologist , and often other health professionals. [ 4 ]


In general, the decision between clipping and coiling is made on the basis of the location of the aneurysm, its size and the condition of the person. Aneurysms of the  middle cerebral artery  and its related vessels are hard to reach with angiography and tend to be amenable to clipping. Those of the  basilar artery  and posterior cerebral artery are hard to reach surgically and are more accessible for endovascular management. [ 58 ]  These approaches are based on general experience, and the only  randomized controlled trial  directly comparing the different modalities was performed in relatively well people with small (less than 10 mm) aneurysms of the  anterior cerebral artery  and  anterior communicating artery  (together the "anterior circulation"), who constitute about 20 percent of all people with aneurysmal SAH. [ 58 ] [ 59 ]  This trial, the  International Subarachnoid Aneurysm Trial  (ISAT), showed that in this group the likelihood of death or being dependent on others for  activities of daily living  was reduced (7.4 percent  absolute risk reduction , 23.5 percent  relative risk  reduction) if endovascular coiling was used as opposed to surgery. [ 58 ]  The main drawback of coiling is the possibility that the aneurysm will recur; this risk is extremely small in the surgical approach. In ISAT, 8.3 percent needed further treatment in the longer term. Hence, people who have undergone coiling are typically followed up for many years afterwards with angiography or other measures to ensure recurrence of aneurysms is identified early. [ 60 ]  Other trials have also found a higher rate of recurrence necessitating further treatments. [ 61 ] [ 62 ]


Vasospasm , in which the blood vessels constrict and thus restrict  blood flow , is a serious complication of SAH. It can cause  ischemic   brain injury  (referred to as "delayed ischemia") and permanent  brain damage  due to lack of oxygen in parts of the brain. [ 63 ]  It can be fatal if severe. Delayed ischemia is characterized by new neurological symptoms, and can be confirmed by  transcranial doppler  or cerebral angiography. About one third of people admitted with subarachnoid hemorrhage will have delayed ischemia, and half of those have permanent damage as a result. [ 63 ]  It is possible to screen for the development of vasospasm with transcranial Doppler every 24–48 hours. A blood flow velocity of more than 120  centimeters per second  is suggestive of vasospasm. [ 30 ]


The pathogenesis of cerebral vasospasm following subarachnoid hemorrhage is attributed to the higher levels of  endothelin 1 , a potent vasoconstrictor, and the lower levels of  endothelial NOS  (eNOS), a potent vasodilator. Both of which are produced from a series of events that begin from the inflammatory reaction caused by the products released from erythrocytes' degradation. Following subarachnoid hemorrhage, different clotting factors and blood products are released into the surrounding  perivascular spaces  known as ( Virchow-Robin spaces ). The released clotting factors like;  fibrinopeptides ,  thromboxane A2  and others lead to microthrombosis around near vessels that leads to extrinsic vasoconstriction of these vessels. Besides that extrinsic vasoconstriction, the erythrocytes' degradation products like;  bilirubin  and  oxyhemoglobin  lead to neuroinflammation that in turn increases the production of  reactive oxygen species  (ROS) which increases and decreases the production of endothelin 1 and endothelial NOS, respectively, the issue that yields in intrinsic vasoconstriction of the neighboring blood vessels and results in cerebral ischemia if left untreated. [ 64 ] [ 65 ] [ 66 ] [ 67 ] [ 68 ]


The use of  calcium channel blockers , thought to be able to prevent the spasm of blood vessels by preventing  calcium  from entering smooth muscle cells, has been proposed for prevention. [ 23 ]  The calcium channel blocker  nimodipine  when taken by mouth improves outcome if given between the fourth and twenty-first day after the bleeding, even if it does not reduce the amount of vasospasm detected on angiography. [ 69 ]  It is the only  Food and Drug Administration  (FDA)-approved drug for treating cerebral vasospasm. [ 26 ]  In  traumatic  subarachnoid hemorrhage, nimodipine does not affect long-term outcome, and is not recommended. [ 70 ]  Other calcium channel blockers and  magnesium sulfate  have been studied, but are not presently recommended; neither is there any evidence that shows benefit if nimodipine is given intravenously. [ 63 ]


Nimodipine is readily authorized in the form of tablets and solution for infusion for the prevention and treatment of complications due to vasospasm following subarachnoid hemorrhage. Another sustained formulation of nimodipine administered via an  external ventricular drain  (EVD), called EG-1962, is also available. In contrast to the tablets and solution formulations of Nimodipine which require an administration every 4hrs for a total of 21 days, the sustained formulation, EG-1962, needs to be administered once directly into the ventricles. The CSF concentrations from EG-1962, however, were at least 2 orders of magnitude higher than those with oral nimodipine. These results supported a phase 3 study that demonstrated a favorable safety profile for EG-1962 but yielded inconclusive efficacy results due to notable differences in clinical outcome based on baseline disease severity. [ 71 ] [ 72 ] [ 73 ]


Some older studies have suggested that  statin  therapy might reduce vasospasm, but a subsequent meta-analysis including further trials did not demonstrate benefit on either vasospasm or outcomes. [ 74 ]  While corticosteroids with mineralocorticoid activity may help prevent vasospasm their use does not appear to change outcomes. [ 75 ]


A protocol referred to as "triple H" is often used as a measure to treat vasospasm when it causes symptoms; this is the use of  intravenous fluids  to achieve a state of  hypertension  (high blood pressure),  hypervolemia  (excess fluid in the circulation), and hemodilution (mild dilution of the blood). [ 76 ]  Evidence for this approach is inconclusive; no randomized controlled trials have been undertaken to demonstrate its effect. [ 77 ]


If the symptoms of delayed ischemia do not improve with medical treatment, angiography may be attempted to identify the sites of vasospasms and administer  vasodilator  medication (drugs that relax the blood vessel wall) directly into the artery.  Angioplasty  (opening the constricted area with a balloon) may also be performed. [ 30 ]


Hydrocephalus  (obstruction of the flow of cerebrospinal fluid) may complicate SAH in both the short and long term. It is detected on CT scanning, on which there is enlargement of the  lateral ventricles . If the level of consciousness is decreased, drainage of the excess fluid is performed by therapeutic lumbar puncture,  extraventricular drain  (a temporary device inserted into one of the ventricles), or occasionally a permanent  shunt . [ 4 ] [ 30 ]  Relief of hydrocephalus can lead to an enormous improvement in a person's condition. [ 11 ]  Fluctuations in blood pressure and  electrolyte imbalance , as well as  pneumonia  and  cardiac decompensation  occur in about half the hospitalized persons with SAH and may worsen prognosis. [ 4 ]   Seizures  occur during the hospital stay in about a third of cases. [ 30 ]


People have often been treated with  preventative   antiepileptic medications . [ 30 ] [ 78 ]  This is controversial and not  based on good evidence . [ 79 ] [ 80 ]  In some studies, use of these medications was associated with a worse prognosis; although it is unclear whether this might be because the drugs themselves actually cause harm, or because they are used more often in persons with a poorer prognosis. [ 81 ] [ 82 ]  There is a possibility of a gastric hemorrhage due to stress ulcers. [ 83 ]


SAH is often associated with a poor outcome. [ 84 ]  The death rate ( mortality ) for SAH is between 40 and 50 percent, [ 28 ]  but trends for survival are improving. [ 4 ]  Of those that survive hospitalization, more than a quarter have significant restrictions in their lifestyle, and less than a fifth have no residual symptoms whatsoever. [ 58 ]  Delay in diagnosis of minor SAH (mistaking the sudden headache for migraine) contributes to poor outcome. [ 29 ]  Factors found on admission that are associated with poorer outcome include poorer neurological grade;  systolic hypertension ; a previous diagnosis of  heart attack  or SAH;  liver disease ; more blood and larger aneurysm on the initial CT scan; location of an aneurysm in the  posterior   circulation ; and higher age. [ 81 ]  Factors that carry a worse prognosis during the hospital stay include occurrence of delayed ischemia resulting from  vasospasm , development of  intracerebral hematoma , or intraventricular hemorrhage (bleeding into the  ventricles  of the brain) and presence of  fever  on the eighth day of admission. [ 81 ]


So-called "angiogram-negative subarachnoid hemorrhage", SAH that does not show an aneurysm with four-vessel angiography, carries a better prognosis than SAH with aneurysm, but it is still associated with a risk of ischemia, rebleeding, and  hydrocephalus . [ 22 ]  Perimesencephalic SAH (bleeding around the  mesencephalon  in the brain), however, has a very low rate of rebleeding or delayed  ischemia , and the prognosis of this subtype is excellent. [ 85 ]


The prognosis of head trauma is thought to be influenced in part by the location and amount of subarachnoid bleeding. [ 23 ]  It is difficult to isolate the effects of SAH from those of other aspects of traumatic brain injury; it is unknown whether the presence of subarachnoid blood actually worsens the prognosis or whether it is merely a sign that a significant trauma has occurred. [ 23 ]  People with moderate and severe traumatic brain injury who have SAH when admitted to a hospital have as much as twice the risk of dying as those who do not. [ 23 ]  They also have a higher risk of severe disability and  persistent vegetative state , and traumatic SAH has been correlated with other markers of poor outcome such as  post traumatic epilepsy , hydrocephalus, and longer stays in the intensive care unit. [ 23 ]   More than 90 percent of people with traumatic subarachnoid bleeding and a Glasgow Coma Score over 12 have a good outcome. [ 23 ]


There is also modest evidence that genetic factors influence the prognosis in SAH. For example, having two copies of ApoE4 (a variant of the gene encoding  apolipoprotein E  that also plays a role in  Alzheimer's disease ) seems to increase risk for delayed ischemia and a worse outcome. [ 86 ]  The occurrence of  hyperglycemia  (high blood sugars) after an episode of SAH confers a higher risk of poor outcome. [ 87 ]


Neurocognitive symptoms, such as  fatigue , mood disturbances, and other related symptoms, are common  sequelae . Even in those who have made good neurological recovery, anxiety, depression,  posttraumatic stress disorder , and cognitive impairment are common; 46 percent of people who have had a subarachnoid hemorrhage have cognitive impairment that affects their quality of life. [ 30 ]  Over 60 percent report frequent headaches. [ 88 ]  Aneurysmal subarachnoid hemorrhage may lead to damage of the  hypothalamus  and the  pituitary gland , two areas of the brain that play a central role in hormonal regulation and production. More than a quarter of people with a previous SAH may develop  hypopituitarism  (deficiencies in one or more of the  hypothalamic–pituitary hormones  such as  growth hormone ,  luteinizing hormone , or  follicle-stimulating hormone ). [ 89 ]  SAH is also associated with  SIADH  and  cerebral salt wasting , and is the most common cause of the latter.


According to a review of 51 studies from 21 countries, the average  incidence  of subarachnoid hemorrhage is 9.1 per 100,000 annually. Studies from Japan and Finland show higher rates in those countries (22.7 and 19.7, respectively), for reasons that are not entirely understood. South and Central America, in contrast, have a rate of 4.2 per 100,000 on average. [ 90 ]


Although the group of people at risk for SAH is younger than the population usually affected by stroke, [ 84 ]  the risk still increases with age. Young people are much less likely than middle-age people (risk ratio 0.1, or 10 percent) to have a subarachnoid hemorrhage. [ 90 ]  The risk continues to rise with age and is 60 percent higher in the very elderly (over 85) than in those between 45 and 55. [ 90 ]  Risk of SAH is about 25 percent higher in women over 55 compared to men the same age, probably reflecting the hormonal changes that result from the  menopause , such as a decrease in  estrogen  levels. [ 90 ]


Genetics may play a role in a person's disposition to SAH; risk is increased three- to fivefold in first-degree relatives of people having had a subarachnoid hemorrhage. [ 3 ]  But lifestyle factors are more important in determining overall risk. [ 84 ]  These risk factors are  smoking , hypertension (high blood pressure), and excessive  alcohol consumption . [ 28 ]  Having smoked in the past confers a doubled risk of SAH compared to those who have never smoked. [ 84 ]  Some protection of uncertain significance is conferred by  caucasian ethnicity ,  hormone replacement therapy , and  diabetes mellitus . [ 84 ]  There is likely an inverse relationship between total serum  cholesterol  and the risk of non-traumatic SAH, though confirmation of this association is hindered by a lack of studies. [ 91 ]  Approximately 4 percent of aneurysmal bleeds occur after  sexual intercourse  and 10 percent of people with SAH are bending over or lifting heavy objects at the onset of their symptoms. [ 11 ]


Overall, about 1 percent of all people have one or more cerebral aneurysms. Most of these are small and unlikely to rupture. [ 52 ]


While the clinical picture of subarachnoid hemorrhage may have been recognized by  Hippocrates , the existence of cerebral aneurysms and the fact that they could rupture was not established until the 18th century. [ 92 ]  The associated symptoms were described in more detail in 1886 by  Edinburgh  physician Dr  Byrom Bramwell . [ 93 ]  In 1924, London  neurologist  Sir  Charles P. Symonds  (1890–1978) gave a complete account of all major symptoms of subarachnoid hemorrhage, and he coined the term "spontaneous subarachnoid hemorrhage". [ 5 ] [ 92 ] [ 94 ]  Symonds also described the use of  lumbar puncture  and  xanthochromia  in diagnosis. [ 95 ]


The first surgical intervention was performed by Norman Dott, who was a pupil of  Harvey Cushing  then working in Edinburgh. He introduced the wrapping of aneurysms in the 1930s, and was an early pioneer in the use of angiograms. [ 5 ]  American  neurosurgeon  Dr  Walter Dandy , working in  Baltimore , was the first to introduce clips in 1938. [ 56 ]   Microsurgery  was applied to aneurysm treatment in 1972 in order to further improve outcomes. [ 96 ]  The 1980s saw the introduction of triple H therapy [ 76 ]  as a treatment for delayed ischemia due to  vasospasm , and trials with nimodipine [ 69 ] [ 97 ]  in an attempt to prevent this complication. In 1983, the Russian neurosurgeon Zubkov and colleagues reported the first use of transluminal balloon angioplasty for vasospasm after aneurysmal SAH. [ 98 ] [ 99 ]  The Italian neurosurgeon Dr Guido Guglielmi introduced his endovascular coil treatment in 1991. [ 6 ] [ 57 ]


The  SurgiScope  is a microscope and robot designed to hold tools and assist in positioning those tools during neurosurgery. The unit is mounted on the ceiling and can hold instruments such as endoscopy tools, biopsy needles, and electrodes. The associated software allows for target and trajectory determination. The SurgiScope has been used for stereotactic guidance and neuronavigation during surgical procedures. [ 1 ] [ 2 ] [ 3 ] [ 4 ]


The  TESSYS method  (transforaminal endoscopic surgical system) is a  minimally-invasive ,  endoscopic spinal procedure  for the treatment of a  herniated disc .
It was a further development of the YESS method by the Dutch Dr Thomas Hoogland in the Alpha Klinik in Munich in 1989 and was first called THESSYS (Thomas Hoogland EndoScopic SYStem). The procedure involves  performing a small foramenotomy and removal of soft tissue compressing the nerve root. [ citation needed ]


With the Tessys method, the  surgeon  removes the herniated portions of the disc using posterior lateral  endoscopic  access. This surgical method for  spinal disc herniations  is especially gentle for the patient. During the procedure, the patient is positioned either in the lateral or prone position, and local anesthetic is administered, usually in combination with sedation. The patient remains responsive, and typically general anesthesia is not necessary. The surgeon removes the herniated disc tissue through an access tube of mere millimeters via the intervertebral foramen. With special instruments, the surgeon progressively and gently dilates to access the disc without disrupting the surrounding muscles or conjunctive tissue. [ 1 ] [ 2 ]


The first blind transforaminal discectomy was done by Parvis Kambin in 1973 with Craig's canula's.
The Tessys method was a further development of the existing YESS method (American  Anthony Yeung ) by the Dutch Thomas Hoogland in 1989 in Munich by reaming a few mm's from the SAP (Superior Articular Process). As of January 2018 [update] , more than 400,000 patients worldwide are operated with the TESSYS method. Most of them with the original joimax reamers or the newer safer MaxMoreSpine drills also developed and patented by Dr Thomas Hoogland [ citation needed ]


The system was introduced in the Netherlands in 2004 under the acronym PTED (Percutaneous Transforaminal Endoscopic Discectomy) by orthopaedic surgeon M. Iprenburg, who has since then successfully used the procedure with over 2600 of hernia patients with the joimax reamers. [ citation needed ]


The Tessys method is suitable for most prolapsed discs, regardless of the anatomical position. Another spinal indication for the Tessys procedure would be cauda equina syndrome, in a case where conservative methods of treatment failed to ameliorate the pain, or if only surrounded nerves are affected. Every intervertebral surgery requires a prior detailed discussion with the patient and imaging diagnostics such as  MRI ,  CT scans  and/or  X-ray . Monitoring of the compressed nerves and associated pathways is indicated due to the proximity of surgical manipulations that are in contact with nerve roots and/or the spinal cord. [ 3 ]  Monitoring modalities indicated are continuous somatosensory evoked potentials and spontaneous electromyography of the muscles supplied by the affected nerve roots. [ 4 ] [ 5 ]  Performing a discogram during the surgery procedure provides additional confirmation of the patient's anatomy and the position of the disc prolapse but might increase the degenerative changes in the disc. . [ 4 ]


To remove a herniated disc, the Tessys method uses a lateral, transforaminal, endoscopic access path via the intervertebral foramen. The surgery takes about 45–75 minutes. During the procedure, the patient is either in the lateral or prone position. The operation is preferable done under analgo-sedation in daysurgery. In Germany patients have however to stay for three days in the hospital to get proper payment from insurance companies. [ citation needed ]


The access to the prolapse is achieved using a three-step guide wire technique: The surgeon gradually dilates through the soft tissue with the aid of  C-arm  radiographic monitoring and stretches the foramen step-by-step, with little or no disturbance to the surrounding muscles and nerves. Utilizing Tessys via nature's entry point, also known as  Kambin's Triangle , preserves the stability of the spinal column. [ citation needed ]


The endoscope features a slim working channel to guide instruments to the anatomy. The surgeon leads the endoscope through the working tube while in surgery. The camera emits pictures and/or video of the operating field to a monitor, while the surgeon uses special surgical instruments to remove the herniated disc material safely, with precision.


Studies document the advantages and the success of minimally invasive endoscopic spine surgery. The US research clinic the Cleveland Foundation agrees that the recovery period in patients treated with the Tessys method is accelerated by several weeks to months in comparison to conventionally treated patients. Many other studies document a success rate of more than 93%. [ 6 ] [ 7 ] [ 8 ] [ 9 ]  In January 2018 more as 3000 publications about endoscopic spine surgery are found in PubMed. Among them 2 RCT's. In the USA a complete new coding system was started for all endoscopic spine procedures. In the Netherlands the procedure was called experimental in 2006.


The  translabyrinthine approach  is a surgical approach to treating serious disorders of the  cerebellopontine angle , (CPA), which is the most common location of posterior fossa tumors. especially  acoustic neuroma . [ 1 ]  In this approach, the  semicircular canals  and  vestibule , including the  utricle  and the  saccule  of the  inner ear  are removed, causing complete hearing loss in the operated ear. The procedure is typically performed by a team of surgeons, including a  neurotologist  (an ear, nose, and throat surgeon specializing in skull base surgery) as well as a  neurosurgeon .


The translabyrinthine approach was developed by  William F. House , M.D., [ 2 ]  who began doing dissections in the laboratory with the aid of magnification and subsequently developed the first  middle cranial fossa  and then the translabyrinthine approach for the removal of acoustic neuroma.


This surgical approach is typically performed by a team of surgeons, including a  neurotologist  (an ear, nose, and throat surgeon specializing in skull base surgery) as well as a  neurosurgeon .


In this approach, the  semicircular canals  and  vestibule , including the  utricle  and the  saccule  of the  inner ear  are removed with a surgical drill, causing complete sensorineural hearing loss in the operated ear.  The facial nerve, which innervates the muscles of the face, is preserved in a higher percentage of cases than with other approaches.


Prior to the translabyrinthine approach, in the early 1960s acoustic neuromas were treated utilizing a suboccipital approach without the aid of an operating microscope. With the introduction of the translabyrinthine approach, mortality rates decreased from 40% in the State of California to 1%.


Transsphenoidal surgery  is a type of  surgery  in which an  endoscope  or  surgical instruments  are inserted into part of the brain by going through the nose and the  sphenoid bone  (a butterfly-shaped bone forming the anterior inferior portion of the  brain case ) into the  sphenoidal sinus  cavity. Transsphenoidal surgery is used to remove  tumors  of the  pituitary gland . (Such tumours, although within the skull, are outside the brain itself).


The transsphenoidal approach was first attempted by  Hermann Schloffer  in 1907. [ 1 ]  Use of the procedure grew in the 1950s and 60s with the introduction of intraoperative  fluoroscopy  and  operating microscope . [ 1 ]


The  transverse sinuses  (left and right lateral sinuses), within the human head, are two areas beneath the brain which allow blood to drain from the back of the head. They run laterally in a  groove  along the interior surface of the  occipital bone . They drain from the  confluence of sinuses  (by the  internal occipital protuberance ) to the  sigmoid sinuses , which ultimately connect to the  internal jugular vein .   See diagram (at right) : labeled under the brain as " SIN. TRANS. " (for Latin:  sinus transversus ).


The transverse sinuses are of large size and begin at the  internal occipital protuberance ; one, generally the right, being the direct continuation of the  superior sagittal sinus , the other of the  straight sinus .


Each transverse sinus passes lateral and forward, describing a slight curve with its convexity upward, to the base of the  petrous portion  of the  temporal bone , and lies, in this part of its course, in the attached margin of the  tentorium cerebelli ; it then leaves the tentorium and curves downward and medialward (an area sometimes referred to as the  sigmoid sinus ) to reach the  jugular foramen , where it ends in the  internal jugular vein .


In its course it rests upon the  squama  of the  occipital , the  mastoid angle  of the  parietal , the  mastoid part  of the  temporal , and, just before its termination, the  jugular process  of the occipital; the portion which occupies the groove on the mastoid part of the temporal is sometimes termed the  sigmoid sinus .


The transverse sinuses are frequently of unequal size, with the one formed by the  superior sagittal sinus  being the larger; they increase in size as they proceed, from back to center.


On transverse section, the horizontal portion exhibits a prismatic form, the curved portion has a semicylindrical form.


They receive the blood from the superior petrosal sinuses at the base of the petrous portion of the temporal bone; they communicate with the veins of the  pericranium  by means of the  mastoid  and  condyloid   emissary veins ; and they receive some of the  inferior cerebral  and  inferior cerebellar veins , and some veins from the  diploë .


The  petrosquamous sinus , when present, runs backward along the junction of the squama and petrous portion of the temporal, and opens into the transverse sinus.


Traumatic pneumorrhachis  is a medical condition in which air has entered the  spinal canal .


Traumatic pneumorrhachis is very rare phenomenon. Only eight cases with pneumorrhachis extending to more than one spinal region had been reported in the literature. [ 1 ] [ 2 ]  Gordon had initially described the phenomenon of intraspinal air. [ 3 ]  The term  pneumorrhachis  was used for the first time by Newbold et al. [ 4 ]  The two subtypes of pneumorrhachis, which includes  epidural  or  subarachnoid , are difficult to distinguish even with  CT scanning . However, the presence of  pneumocephalus  goes more in favor of subarachnoid subtype. Goh and Yeo in their study have reported that the epidural pneumorrhachis is self-limited, whereas the more common subarachnoid pneumorrhachis type may be complicated by  tension pneumocephalus  and  meningitis . [ 5 ]  Traumatic subarachnoid pneumorrhachis is almost always secondary to major trauma and is a marker of a severe injury. For example, air may migrate via the neural foramina behind the driving pressure of pneumothorax. [ 2 ]  The pathophysiology described for it states that the penetrated air, which had led to the formation of pneumocephalus might have been forced caudally due to the raised intracranial pressure as a consequence of severe brain injury and patient's horizontal position allowing the entrapped air to pass through the  foramen magnum  into the spinal canal. Due to its rareness, asymptomatic presentation and myriad etiologies, no guidelines for its treatment or care has been described. Pneumorrhachis typically resolves spontaneously but occasionally it can have serious complications. Patient with subarachnoid pneumorrhachis should be treated meticulously and a temporary lumbar drainage may be required if they have concomitant  cerebro-spinal fluid  leak. [ 6 ]


A  vagotomy  is a  surgical  procedure that involves  removing part of  the  vagus nerve . It is performed in the  abdomen .


A plain vagotomy eliminates afferent and  parasympathetic  innervation of the stomach and the left side of the  transverse colon .  Other techniques focus on branches leading from the retroperitoneum to the stomach. [ 1 ]


Highly selective vagotomy  refers to denervation of only those branches supplying the lower esophagus and stomach (leaving the  nerve of Latarjet  in place to ensure the emptying function of the stomach remains intact). It is one of the treatments of peptic ulcer.


Vagotomy can be used in the surgical management of peptic (duodenal and gastric) ulcer disease (PUD). Vagotomy was once commonly performed to treat and prevent PUD; however, with the availability of excellent acid secretion control with H2 receptor antagonists, such as cimetidine, ranitidine, and famotidine, and proton pump inhibitors (PPIs), such as pantoprazole, rabeprazole, omeprazole, and lansoprazole, the need for surgical management of peptic ulcer disease has greatly decreased. [ 2 ]


The basic types of vagotomy are:


All types of vagotomy can be performed at open surgery (laparotomy) or using minimally invasive surgery (laparoscopy).


For the management of PUD, vagotomy is sometimes combined with  antrectomy  (removal of the distal half of the stomach) to reduce the rate of recurrence. Reconstruction is performed with gastroduodenostomy (Billroth I) or gastrojejunostomy (Billroth II).  It is left intact in highly selective vagotomy so the function of gastric emptying remains intact. [ 4 ]


Truncal vagotomy is a treatment option for chronic duodenal ulcers. [ 5 ] [ 6 ]  It was once considered the gold standard, but is now usually reserved for patients who have failed the first-line "triple therapy" against  Helicobacter pylori  infection: two antibiotics ( clarithromycin  and  amoxicillin  or  metronidazole ) and a  proton pump inhibitor  (e.g.,  omeprazole ). It is also used in the treatment of  gastric outlet obstruction . [ 7 ] [ 8 ]


In 2007, the use of vagotomy to treat  obesity  was being studied. [ 9 ]  The vagus nerve provides  efferent nervous signals  out from the hunger and satiety centers of the  hypothalamus , a region of the brain central to the regulation of food intake and energy expenditure. [ 10 ]  The circuit begins with an area of the hypothalamus, the  arcuate nucleus , which has outputs to the  lateral hypothalamus  (LH) and  ventromedial hypothalamus  (VMH), the brain's feeding and satiety centers, respectively. [ 11 ] [ 12 ]


Animals with lesioned VMH will gain weight even in the face of severe restrictions imposed on their food intake, because they no longer provide the signaling needed to turn off energy storage and facilitate energy expenditure and fat burning.


In humans, the VMH is sometimes injured by ongoing treatment for  acute lymphoblastic leukemia  or surgery or radiation to treat  posterior cranial fossa  tumors. [ 10 ]  Disabling the VMH renders it unresponsive to peripheral energy balance signals; this, in turn, suppresses sympathetic activity (which leads to malaise and decreased energy expenditure) and stimulates vagal activity (which augments  insulin  production and  adipogenesis  (fat cell expansion)). [ 13 ]  Research shows that VMH dysfunction affects both energy intake and energy expenditure and is associated with constant weight gain, which results from a chronic positive energy balance caused by excessive energy intake and reduced metabolic rate.  In the past, adrenergic or serotonergic agonists were investigated for the treatment of obesity by suppressing appetite and stimulating thermogenesis, but neither calorie restriction nor treatment with these thermogenic agents has been very successful in achieving and maintaining weight reduction. [ 10 ]  The vagus nerve is thought to be one key mediator of these effects, as lesions lead to chronic elevations in insulin secretion, inhibiting fat oxidation and promoting energy storage in adipocytes.
Vagotomy may have an impact upon  ghrelin . [ 14 ]  In an open-label, prospective study of 30 obese patients (26 women), response has been variable; the intervention has generally been safe, although  adverse events  have included  gastric dumping syndrome  (n=3), wound infection (n=2), other (n=5), and diarrhea (n=6). [ 15 ]


Vagotomy was once popular as a way of treating and preventing PUD [ 16 ]  and subsequent  ulcer perforations . [ 17 ] [ 18 ]   PUD  was thought to be due to excess secretion of the acid environment in the  stomach , or at least that PUD was made worse by hyperacidity. Vagotomy was a way to reduce the acidity of the stomach, by denervating the parietal cells that produce acid. This was done with the hope that it would treat or prevent peptic ulcers. It also had the effect of reducing or eliminating symptoms of  gastroesophageal reflux  in those who suffered from it. The incidence of vagotomy decreased following the discovery by  Barry Marshall  and  Robin Warren  that  H. pylori  is responsible for most peptic ulcers, because  H. pylori  can be treated much less invasively. One potential side effect of vagotomy is a  vitamin B 12  deficiency. As vagotomy decreases gastric secretion,  intrinsic factor  production can be impaired. Intrinsic factor is needed to absorb vitamin B 12  efficiently from food, and injections or large oral doses of the vitamin may be required after such a procedure in certain populations. [ 19 ]


Vasospasm  refers to a condition in which an  arterial   spasm  leads to  vasoconstriction . This can lead to tissue  ischemia  (insufficient blood flow) and tissue death ( necrosis ).


Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to  atherosclerosis . Vasospasm is the major cause of  Prinzmetal's angina .


Cerebral vasospasm may arise in the context of  subarachnoid hemorrhage  as symptomatic vasospasm (or delayed  cerebral ischemia ), where it is a major contributor to post-operative stroke and mortality. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage, however the relationship between radiological arterial spasm (seen on angiography) and clinical neurological deterioration is nuanced and uncertain.  [ 1 ]


Normally  endothelial cells  release  prostacyclin  and  nitric oxide  (NO) which induce relaxation of the  smooth muscle  cells, and reduce aggregation of  platelets . [ 2 ]  Aggregating platelets stimulate  ADP  to act on endothelial cells and help them induce relaxation of the smooth muscle cells. However, aggregating platelets also stimulate  thromboxane A2  and  serotonin  which can induce contraction of the smooth muscle cells.  In general, the relaxations outweighs the contractions.


In atherosclerosis, a dysfunctional endothelium is observed on examination. It does not stimulate as much prostacyclin and NO to induce relaxation on smooth muscle cells. Also there is not as much inhibition of aggregation of platelets. In this case, the greater aggregation of platelets produce ADP, serotonin, and thromboxane A2. However the serotonin and the thromboxane A2 cause more contraction of the smooth muscle cells and as a result contractions outweigh the relaxations. [ 3 ] [ 4 ] [ 5 ]


Vasospasm can occur in a wide variety of peripheral vascular beds under poorly understood mechanisms. Prinzmetal angina, Buerger's disease, contrast mediated selective renal vasospasm, hypercoagulability and cryoglobulinemia likely represent just a few of the known pieces of this puzzling phenomena. Ischemia in the heart due to prolonged  coronary vasospasm  can lead to  angina ,  myocardial infarction  and even death. Vasospasm in the hands and fingers due to prolonged exposure to vibration (30 – 300 Hz) [ failed verification ] [ dubious  –  discuss ]  and triggered by cold can lead to  Hand-arm vibration syndrome  in which feeling and manual dexterity are lost. [ 6 ]


In angiography, vascular access through femoral and axillary arteries are preferred because they are less prone to vasospasm. Meanwhile, brachial artery is more prone to vasospasm during instrumental access. [ 7 ]


In a case study in 2000, following surgery for head trauma, a patient developed mild  hypothermia , a typical defense mechanism the brain uses to protect itself after injury. After the hypothermia rewarming period, the patient died from increased intracranial pressure and  anisocoria . A sample of the cerebrospinal fluid and autopsy results indicated cerebral vasospasm. [ 8 ]


The occurrence of vasospasm can be reduced by preventing the occurrence of  atherosclerosis . This can be done in several ways, the most important being lifestyle modifications—decreasing  low-density lipoprotein  (LDL),  quitting smoking ,  physical activity , and control for other risk factors including  diabetes ,  obesity , and  hypertension .  Pharmacological therapies  include  hypolipidemic agents ,  thrombolytics  and  anticoagulants . Pharmacological options for reducing the severity and occurrence of  ischemic episodes  include the  organic nitrates , which are rapidly metabolized to release  nitric oxide  in many tissues, [ 9 ]  and are classified as having either long-acting (i.e.  isosorbide dinitrate ) or short-acting (i.e.  nitroglycerin ) durations of action.


These drugs work by increasing  nitric oxide  levels in the blood and inducing coronary  vasodilation  which will allow for more coronary blood flow due to a decreased coronary resistance, allowing for increased oxygen supply to the vital organs (myocardium). The nitric oxide increase in the blood resulting from these drugs also causes dilation of systemic veins which in turn causes a reduction in venous return, ventricular work load and ventricular radius. All of these reductions contribute to the decrease in ventricular wall stress which is significant because this causes the demand of oxygen to decrease. In general organic nitrates decrease oxygen demand and increase oxygen supply. It is this favourable change to the body that can decrease the severity of ischemic symptoms, particularly angina.


Other medications used to reduce the occurrence and severity of vasospasm and ultimately ischemia include  L-type   calcium channel blockers  (notably  nimodipine , as well as  verapamil ,  diltiazem ,  nifedipine ) and beta-receptor antagonists (more commonly known as  beta blockers  or β-blockers) such as  propranolol .


L-type calcium channel blockers can induce dilation of the coronary arteries while also decreasing the heart's demand for oxygen by reducing  contractility , heart rate, and wall stress. The reduction of these latter three factors decreases the contractile force that the myocardium must exert in order to achieve the same level of  cardiac output .


Beta-receptor antagonists do not cause vasodilation, but like L-type calcium channel blockers, they do reduce the heart's demand for oxygen. This reduction similarly results from a decrease in heart rate, afterload, and wall stress.


Like most pharmacological therapeutic options, there are risks that should be considered. For these drugs in particular, vasodilation can be associated with some adverse effects which might include orthostatic hypotension, reflex  tachycardia , headaches and palpitations. Tolerance may also develop over time due compensatory response of the body, as well as depletion of -SH groups of glutathione which are essential for the metabolism of the drugs to their active forms.


Potential side effects:


Organic nitrates should not be taken with  PDE5  inhibitors (i.e.  sildenafil ) since both NO and PDE5 inhibitors increase  cyclic GMP  levels and the sum of their pharmacodynamic effects will greatly exceed the optimal therapeutic levels. What you could see upon taking both medications at the same time, as caused by the much higher induction of relaxation of smooth muscle cells, include a severe drop in blood pressure.


Beta-receptor antagonists should be avoided in patients with reactive pulmonary disease to avoid asthma attacks. Also Beta-receptor antagonists should be avoided in patients with AV node dysfunction and/or patients on other medications which might cause bradycardia (i.e. calcium channel blockers). The potential for these contraindications and drug-drug interaction could lead to asystole and cardiac arrest.


Certain calcium channel blocker should be avoided with some beta-receptor blockers since they may cause severe bradycardia and other potential side effects.


Since vasospasms can be caused by atherosclerosis and contribute to the severity of ischemia there are some surgical options which can restore circulation to these ischemic areas. Regarding coronary vasospasm, one surgical intervention, referred to as percutaneous coronary intervention or angioplasty, involves placing a  stent  at the site of stenosis in an artery and inflating the stent using a balloon catheter. Another surgical intervention is  coronary artery bypass .


Vertebral fixation  (also known as "spinal fixation") is an  orthopedic surgical  procedure in which two or more  vertebrae  are anchored to each other through a synthetic " vertebral fixation device ", with the aim of reducing vertebral mobility and thus avoiding possible damage to the  spinal cord  and/or  spinal roots .


A vertebral fixation procedure may be indicated in cases of  vertebral fracture ,  vertebral deformity , or degenerative vertebral disorders (such as  spondylolisthesis ).


The device used to achieve vertebral fixation is usually a permanent rigid or semi-rigid  prosthesis  made of  titanium ; examples include rods, plates, screws, and various combinations thereof. A less common alternative is the use of a resorbable fixation device, composed of a bio-resorbable material.


The medical community uses several different techniques for stabilizing the posterior region of the  spine .  The most radical of these techniques is  spinal fusion .  In recent years/decades spinal  surgeons  have begun to rely more heavily on mechanical implants, which provide increased stability without so severely limiting the recipient's range of motion.  A number of devices have been developed that allow the recipients near natural range of motion while still providing some support.  In many cases the support offered by such devices is insufficient, leaving the  physician  with few other choices than spinal fusion.


A spinal fixation device stabilizes an area of the  posterior spine  while allowing for a significant range of motion and limiting the compression of the affected  vertebrae .  The device consists of two or more arm assemblies (lateral) connected by one or more telescopic assemblies (vertical).  Each arm assembly is composed of a central portion, which connects to the telescopic assembly or assemblies. Left and right arms attach to the corresponding side of the central portion of the arm assembly.  Each arm section is directly connected to its individual pedicle by means of pedicle fasteners.


More information about this specific spinal fixation device can be found in  The United States Patent Service's  November 13, 2007 publication of new patents.  This patent can currently (September 23, 2008) be found on  The U.S. Patent Website . [ 1 ]


White matter dissection  refers to a special anatomical technique able to reveal the subcortical organization of white matter fibers in the human or animal cadaver brain.


The first studies of cerebral  white matter  (WM) were described by  Galen  and by the subsequent efforts of  Vesalius  on human cadaver specimens. [ 2 ] [ 3 ]  The interest for the deep anatomy of the brain  pushed anatomist during centuries to create and develop different techniques  for specimen preparation and dissection in order to better reveal the complex white matter architectural organization. [ 2 ] [ 3 ] [ 4 ] [ 5 ]


However, the biggest impact on the dissection of white matter anatomy was made by  Joseph Klingler who developed a new method for specimens preparation and dissection. This technique became more feasible and widely used  due to an increased  quality of dissection and surprising quality of anatomical details. [ 4 ] [ 5 ] [ 6 ] [ 7 ]  Klingler developed a new method of brain fixation, by freezing already formalin-fixed brains before dissection. [ 6 ] [ 7 ]  First, the water crystallization induced by freezing disrupts the structure of the grey matter (which has a high water content). This process made possible to peel off the cortex from the brain surface without damaging the subcortical white matter organization underneath. Second, the freezing process along the WM fibers, induced a clear separation between them facilitating the dissection by progressive peeling of the fibers. [ 4 ] [ 8 ] [ 9 ]


White matter fibre dissection is nowadays considered as a valuable tool to enhance our knowledge about brain connectivity, [ 5 ] [ 9 ] [ 10 ] [ 1 ]  and has been used to validate  tractographic  results and vice versa with good consistency between the two techniques, [ 11 ]  but also for neurosurgical training and neuroanatomical teaching.


Plastic surgery  is a surgical specialty involving the restoration, reconstruction, or alteration of the human body. It can be divided into two main categories:  reconstructive surgery  and  cosmetic surgery .  Reconstructive surgery  covers a wide range of specialties, including  craniofacial surgery ,  hand surgery ,  microsurgery , and the treatment of  burns . This category of surgery focuses on restoring a body part or improving its function. In contrast,  cosmetic (or aesthetic) surgery  focuses solely on improving the physical appearance of the body. [ 1 ] [ 2 ]  A comprehensive definition of plastic surgery has never been established, because it has no distinct anatomical object and thus overlaps with practically all other surgical specialties. An essential feature of plastic surgery is that it involves the treatment of conditions that require or may require tissue relocation skills.


The word  plastic  in  plastic surgery  is in reference to the concept of "reshaping" and comes from the Greek πλαστική (τέχνη),  plastikē  ( tekhnē ), "the art of modelling" of  malleable   flesh . [ 3 ]   This meaning in English is seen as early as 1598. [ 4 ]  In the surgical context, the word "plastic" first appeared in 1816 and was established in 1838 by Eduard Zeis, [ 5 ]  preceding the modern technical usage of the word as "engineering material made from  petroleum " by 70 years. [ 6 ]


Treatments for the plastic repair of a broken nose are first mentioned in the  c.  1600 BC  Egyptian medical text called the  Edwin Smith papyrus . [ 8 ] [ 9 ]  The early trauma  surgery  textbook was named after the American  Egyptologist , Edwin Smith. [ 9 ]  Reconstructive surgery techniques were being carried out in  India  by 800 BC. [ 10 ]   Sushruta  was a  physician  who made contributions to the field of plastic and  cataract  surgery in the 6th century BC. [ 11 ]


The  Romans  also performed plastic cosmetic  surgery , using simple techniques, such as repairing damaged ears, from around the 1st century BC. [ 12 ]  For religious reasons, they did not  dissect  either human beings or animals, thus, their knowledge was based in its entirety on the texts of their  Greek  predecessors. Notwithstanding,  Aulus Cornelius Celsus  left some accurate  anatomical  descriptions, [ 13 ]  some of which—for instance, his studies on the  genitalia  and the  skeleton —are of special interest to plastic surgery. [ 14 ]


Several ancient Sanskrit medical treatise mentions some types of plastic surgery in India such as the works of  Sushruta  and  Charaka . These works were translated into the  Arabic language  during the  Abbasid  Caliphate in 750 AD. [ 15 ]  The Arabic translations made their way into  Europe  via intermediaries. [ 15 ]  In  Italy , the Branca family [ 16 ]  of  Sicily  and  Gaspare Tagliacozzi  ( Bologna ) became familiar with the techniques of Sushruta. [ 15 ]


All fields of surgery, the  Arab  physician, surgeon, and chemist  Al-Zahrawi  talks of the use of silk thread suture to achieve good  cosmesis . He describes what is thought to be the first attempt at  reduction mammaplasty  for the management of  gynaecomastia . He gives detailed descriptions of other basic surgical techniques such as  cautery  and wound management. [ 17 ]