Deep brain stimulator (DBS) placement is a minimally invasive procedure that involves placement of electrodes into deep brain structures using microelectrode recordings and macrostimulation findings [1]. These electrodes are then connected to an implantable pulse generator (IPG), which is usually placed in the subclavicular region [1]. DBS is an effective treatment modality for a variety of movement disorders such as Parkinson disease, essential tremor, dystonia [1,2,3] and has expanded as a method of treatment for other disorders such as chronic pain, and other cognitive disorders including Alzheimer's disease (AD) and Huntington's chorea [3,4,5,6]. There are four main components to the deep brain stimulator which include: (1) the intracranial electrodes that are inserted surgically into the deep brain gray matter (2) an anchoring system (plastic ring) that fixes the electrode, (3) a single or double channel IPG and (4) an extension cable that connects the DBS electrodes to the pulse generator which is implanted in the chest wall or abdomen [7,8]. This procedure can be performed in a single surgical day or can be staged, with the connection of the pulse generator and electrodes done on another day. The aim of this review article is to discuss the nuances and practical issues that are faced while administering anesthesia during DBS surgery.

While evaluating a patient for DBS surgery, it is important to weigh the overall benefits to the risk associated with the surgery. Careful patient selection by both the surgical and anesthesia teams is essential. It is critical that the anesthesia provider evaluates each patient's co-morbidities as well as the patient's primary disease specific considerations. It is also important to evaluate each patient for anesthetic considerations for the procedure.

In addition to anesthesia, patients should be evaluated in terms of their family and social support. It is crucial for the patients to understand the risks and demands associated with different stages of surgery and to be able to comply with them. Patients and their family members should be educated regarding the immediate post-operative outcomes, complications, reasonable long term outcomes and peri-operative medications management. The need for multiple programming sessions and medications adjustment to achieve optimum clinical outcome should also be informed well in advance so as to have cooperation of the patient and their family. All the queries, doubts and expectations should also be resolved prior to surgery to relieve the anxiety and stress associated with an awake surgical procedure.

Neuropsychological assessment is recommended and should include assessment of cognitive functions, mood disorders including other neuropsychiatric symptoms, family support, and realistic expectations [16,17]. Patients with severe dementia or other neuropsychiatric symptoms should be deferred from DBS surgery and underlying condition should be addressed first. However, patients with mild cognitive dysfunction or frontal lobe dysexecutive syndrome may still undergo surgery but should receive extra counseling along with their family regarding the potential for increased risk of cognitive impairment and confusion post-surgery [16,17,18]. Neuropsychiatric disorders such as anxiety, major depression, and mania must be identified and medically optimized preoperatively and an intra-operative anxiety counselor can also be arranged. DBS surgery in patients with psychotic disorders or severe personality disorders should be avoided.

Cardiac, pulmonary, and systemic conditions such as hypertension, diabetes and cancer should be stabilized prior to DBS surgery. Patients who are on chronic anti-platelet or Coumadin therapy must be able to tolerate complete withdrawal from these medications prior to surgery. Consultation with other medical specialists (e.g., cardiologists, pulmonologist, hematologist, nephrologist, and urologist) may be required in some patients prior to surgery.

Airway management of patients undergoing DBS placement can be challenging yet an important task. Having the operating room table placed 180 degrees away from the anesthesia provider decreases airway accessibility. If a stereotactic frame is placed, the standard adult anesthesia circuit face mask cannot be utilized. In an emergency airway situation, management involves either the use of a pediatric face mask or laryngeal mask airway or removal of the frame. For this reason, any patient undergoing sedation for all or part of the procedure should have an advanced airway management plan in place [1]. Patients with co-morbidities such as obstructive sleep apnea, psychiatric disorders, or chronic pain will require special considerations and management. In Fig. 1, a tourniquet is used to aid the anesthesia provider in a hands free chin-lift to prevent airway obstruction. Patients with underlying Parkinson's disease or Dystonia are at higher risk for aspiration pneumonia and laryngospasm due to laryngo-pharyngeal dysfunction and dystonia [1]. Khatib et al. [19] reported an incidence of 1.60% (n = 258) of airway complications that include airway obstruction, prolonged intubation, postoperative acute respiratory distress syndrome, nosocomial pneumonia, or aspiration during DBS implantation surgery [19]. Similarly, Venkatraghavan et al. [20] experienced an incidence of 1.1% (n = 172) complications of airway obstruction and respiratory distress following DBS surgery [20].

MER are done by the neurophysiology team in order to detect and amplify individual neuronal activity at three primary target sites; subthalamic nuclei (STN), GPi, and the ventralis intermedius nucleus of the thalamus (Vim) [1]. Different anesthetic agents can decrease MER by lowering or eliminating spontaneous neuronal firing [21], and suppress motor signs such tremors and rigidity [22]. Since anesthetic drugs work differently on each region of the brain, the extent to which drugs influence MER are unknown [23].

Propofol is a common and frequently used anesthetic drug for sedation in deep brain stimulator cases due to its rapid onset of anesthesia and its rapid reversal [24]. In diseases such as dystonia or Parkinson's disease, propofol has been shown to cause differences in neuronal activity patterns [25,26,27]. MER can be extremely difficult with the use of propofol due to the drug's GABA receptor-mediated sensitivity in subcortical areas of the brain [21,27,28]. Intra-operative testing can be hindered or misinterpreted by the ability of propofol to suppress tremors [27,29], and induce dyskinesias [30,31]. Use of propofol has been associated with sneezing, which can increase intracranial pressure and lead to intracranial hemorrhage [7,32,33]. Although, propofol can interfere with MER, Raz et al. [34] reported that it can be used safely throughout the placement of the stereotactic frame, skin incision, burr hole and the electrical activity returned to baseline after 9.3 ± 4.0 minutes (mean ± 2SDs, n = 24) of stopping the propofol prior to mapping [34].

Dexmedetomidine is more recently seen as the drug of choice for sedation in DBS procedures, being used alone or in conjunction with Propofol. Dexmedetomidine is an alpha-2-adrenergic agonist that causes sedation by acting on the subcortical areas, resembling natural sleep without causing respiratory depression [35]. In addition to its analgesic properties, and ability to decrease arterial blood pressure, it does not affect MER since it has a non-GABA-mediated mechanism of action [36].

Although, the use of a conscious sedation technique with both propofol and dexmedetomidine is preferred, individuals that cannot tolerate an awake technique such as pediatric patients, patients with psychiatric disorders, patients with extreme confusion, claustrophobia, severe anxiety with associated hypertension, and those with extreme pain due to dystonia may require a general anesthesia. The utility of scalp nerve blocks with local anesthetics have been described in various neurosurgical procedures [37]. A combination of scalp blocks and opioids continuous infusion (fentanyl and propofol) can also be used for maintaining conscious sedation in patients undergoing DBS surgery for PD without interfering with the MER [38].

Chen et al. [2] showed that a general anesthetic technique with the use of desflurane was an acceptable alternative anesthetic approach, with comparable motor outcomes to the conscious sedation technique in Parkinson's patients undergoing DBS implantation surgery. However, they found statistically significant deterioration of cognitive function in the general anesthesia group (P = 0.017) [2].

Arterial hypertension during surgery has been associated with intracranial bleeding [7]. This complication can be controlled through a pre- and intraoperative antihypertensive therapy. Adequate pain control, patient positioning, thermal control, and prevention of bladder distension with the use of a Foley catheter as well as avoidance of excessive fluid administration help to control the blood pressure during surgery [7]. Khatib et al. [19] reported a 2.8% incidence of intracranial hemorrhage (n = 258) and a cardiovascular complication rate of 0.40%, which included new onset angina, congestive heart failure and systemic arterial hypertension in patients who underwent DBS implantation surgery [19]. Intracranial hemorrhage due to uncontrolled hypertension during surgery is a devastating complication that can result in permanent neurological deficit [39]. To minimize the risks of intracranial hemorrhage, the anesthesia providers should screen patients for preoperative uncontrolled hypertension, coagulopathy, or recent use of antiplatelet medications [7]. Should bleeding occur intra-operatively, immediate airway stabilization and urgent brain imaging (CT or MRI) must be performed [7].

During the second stage, the DBS lead is connected to an extension wire which is tunneled from the scalp to the subclavicular region and is connected to an IPG [1]. This is typically performed anywhere from two days to three weeks after the initial procedure. This part of the procedure can be done under general anesthesia since microelectrode recordings are not required. Like with any case of general anesthesia, the patients' underlying pathology, co-morbidities, medications and risk factors for a difficult airway or aspiration should be taken into consideration.

When using electrocautery during the second stage or any subsequent surgery in a patient who has a DBS implantable device, it is important to turn off the pulse generator to avoid thermal injury to the brain tissue, reprogramming or damage to the device and its leads [40,41]. During surgery, bipolar electrocoagulation should be used to reduce electromagnetic interference, and the device should be interrogated postoperatively [42]. DBS programming is typically done 4 weeks after the 1st stage of surgery to avoid the "microlesion" effect, in which possible edema formed around the implanted electrode causes improvement of patient symptoms and thus impairs the ability to detect stimulation-induced benefits [15].

Although, DBS placement and research have been done for years in adults, research pertaining to children is recent and very limited. This being said, Sebeo et al. [24] safely performed DBS implantation surgery in 28 pediatric patients (ages 7-17) with dystonia using combined propofol and dexmedetomidine sedation technique [24]. Their only major complication was a case of venous air embolism following the burr-hole placement. The procedure was aborted, and safely performed a month later [24]. The 3.6% incidence rate reported by the authors is similar to the average reported rate for this procedure [43]. Even though, the sedation technique can be applied successfully in the pediatric population, a careful patient selection should be performed.

Successful placement of a DBS device have been described in a 5 year-old child with dystonic storm under general anesthesia [44]. Due to tense masseter muscles and nasopharyngeal dystonia, such patients are likely to present with a difficult airway requiring special techniques including fiberoptic intubation [44].

AD belongs to the group of neurodegenerative disorders, dementia of Alzheimer's disease being the most common form of dementia. It is associated with progressive cognitive impairment encountering short term and long term memory loss [45]. General anesthetics may worsen the course of AD, and the detrimental effects are partially explained by suppression of acetylcholine (Ach) release in the brain [46]. This detrimental effects of anesthetic drugs are more pronounced with the use of volatile inhalation agents such as desflurane and sevoflurane [47,48,49]. Caution should be used when performing a general anesthesia for DBS implantation surgery in patients with AD, so as not to further decrease their cognitive function or cause delirium in a patient with an already compromised central cholinergic neuronal transmission [50,51]. The safety threshold of propofol is higher [51], possibly making it a safer alternative for a cooperative AD patient.

Dr. George Williams [52] from the University of Texas-Medical School had an elderly male presenting with conductive hearing loss in the pre-operative area for an urgent procedure [52]. This gentleman was unable to respond to any auditory instructions unless they were given by the familiar voice of his wife. Dr. Williams, with permission, recorded the wife's voice giving simple commands such as "wiggle your toes" and "take a deep breath" on his I-phone [52]. Dr. Williams then placed his phone by the patient's dominate ear in which the patient responded only to commands that were given by the familiar voice of his wife [52]. Many times individuals can only follow the command of the voices of their caregivers. The use of technological advancements allow for the pre-recording of familiar voices in order to have the patient be able to communicate and participate in their procedure and MER testing.

Special consideration needs to be taken with patients that have pacemakers. In past, deep brain stimulator was contraindicated in patients with cardiac pacemakers because of their possible negative interaction with each other [7]. Ozben et al. [53] have proven that a bipolar configuration of DBS and cardiac pacemakers are less prone to interaction and can be used together [53,54]. Pre-operatively, cardiac pacemakers should be interrogated and placed in a bipolar mode for sensing and stimulation to minimize interference [55]. MRI testing is contraindicated with most pacemakers so a stereotactic CT should be used for imaging [55]. Pulse generators should be implanted as far away from a cardiac pacemakers as possible to minimize the possibilities of interference, and when initially programing the DBS, close observation of the ECG should be observed for interference [56].

The Medtronic O-arm is a portable CT scanner that can be positioned around the patient's head throughout the procedure to provide intraoperative 3-dimensional confirmation of electrode tip locations, see Fig. 2 [57]. With this technique the patient can be placed under general anesthesia with an endotracheal tube. Upon arrival to the operating room the patient is intubated and, after securing the airway, the stereotactic frame may be placed. Like the awake technique, it is important to maintain tight blood pressure control during the procedure as well as during emergency in order to prevent intracranial bleeding.

Venous air embolism (VAE) is a complication that can occur at any time during the placement of a DBS. The complication can occur in both the supine, semi-sitting positions, and sitting position. Two major contributors of VAE are partial airway obstruction due to sedation and hypovolemia from perioperative fasting [4]. The most common initial symptom in an awake patient is coughing or sighing followed by tachypnea, hypoxemia, chest discomfort, tachycardia and hypotension [43]. In order to prevent this complication, the anesthesia provider should limit the extent of head elevation and warrant adequate hydration before the procedure [43]. If a VAE is suspected, the patient should be placed in Trendelenburg position, the surgical site should be irrigated, bone wax applied to any exposed edges, and any open vessels should be cauterized [43]. According to Palmon et al. [58], air aspiration can be attempted through a central line and rapid fluid administration and inotrope support may be used to maintain adequate perfusion and support the patients' blood pressure.

Seizures are another complication that can occur during DBS and should be managed with benzodiazepines or propofol for their termination [7]. Venkatraghavan et al. [20] reported a seizure incidence of 4.5% (n = 172) [20], while Khatib et al. [19] described an incidence of 0.80% among 258 patients [19]. Anesthesia providers should also be aware of the possibility of an akinetic crisis which is typically found in patients with severe Parkinson's disease, in which the patient is alert and conscious, but is unable to communicate [59].

DBS is a safe, effective and well established treatment for movement disorders and epilepsy, and is being explored for the treatment of psychiatric disorders. With the rapid expansion of the horizons of functional neurosurgery, it is prudent for the anesthesiologist to be aware of the intricate details and the requirements of such procedures. Moreover, the extremes of age groups on which such procedures are performed add to the risks and complications associated with both the surgical procedure and the anesthesia. Therefore, appropriate understanding of the preoperative evaluation, intraoperative assessment and postoperative management in such patients undergoing deep brain stimulator implantation surgery results in outstanding outcomes.