Deep brain stimulation (DBS) is a functional non-lesioning neurosurgical technique involving the implantation of electrodes in specific brain regions connected to a pulse generator, allowing for controlled electrical stimulation to the targeted brain region.¹ It represents a crucial milestone in the advancement of surgical treatment for movement disorders. Initially developed in the 1980s when electrical stimulation of the ventral intermediate thalamic nucleus (VIM) improved tremor in patients with Parkinson’s disease (PD), DBS has evolved over time and proven its efficacy in addressing a wide range of movement disorders.²

The established indications for DBS include PD, essential tremor (ET) and dystonia.³ It stands as a viable treatment option particularly for those who are refractory to conventional therapies. The field of its application continues to expand, and over the past two decades, it has encompassed the treatment of diverse neurological disorders, including Tourette’s syndrome, obsessive-compulsive disorder (OCD), epilepsy, dyskinetic cerebral palsy and chronic pain, among others.^{4,5,6,7,8,9,10,11}

The selection of ideal targets for DBS varies across different conditions and remains a topic of ongoing debate.^12,13 Thalamic DBS first emerged in the early 1990s and was shown to be efficacious in the treatment of essential and parkinsonian tremor. It was not long before the targets of subthalamic nucleus (STN) and globus pallidus internus (GPi) were explored. At present, the STN and GPi stand as the most commonly used targets for treatment of PD.² STN DBS has the advantage of allowing a reduction in dopaminergic medication, while GPi was reported to have a better antidyskinetic effect.^13,14,15 Both, however, were shown to be equally effective in improving the motor symptoms of PD.¹⁴ Following its success, thalamic DBS for essential tremor and PD-related tremor secured Food and Drug Administration approval in 1997.¹⁶ Subsequently, in 2003, both STN and GPi DBS gained approval for treating PD.¹⁷

Despite its success, the exact mechanism of DBS remains unclear. It is hypothesised that DBS exerts its therapeutic effects by overriding the irregular, pathological activity from the stimulation target and replacing it with a stimulus-induced regular pattern.²

Pathway

Established in 2021, the National DBS Service Ireland is based at Beaumont Hospital and Mater University Hospital, Dublin and caters to a diverse range of patients in need of DBS for various neurological conditions. Potential candidates for the surgery are typically referred to the service by their attending neurologist. After the referral, the patient undergoes a comprehensive assessment conducted by a multidisciplinary team, including a neurologist, neuropsychologist, speech and language therapist (SALT), and physiotherapist. This assessment covers aspects of diagnosis, co-morbidities, cognitive function, as well as psychiatric wellbeing. The findings are then discussed at a multidisciplinary team meeting and, if deemed suitable, the candidate is subsequently referred to a neurosurgeon and anaesthesiologist for pre-operative surgical planning.

Careful patient selection is crucial for the success of DBS surgery. The evaluation of a patient’s suitability for surgery encompasses not only patient-specific medical conditions which may increase the surgical risk, but also considers different factors that may limit the therapeutic benefits from DBS.¹⁸ The primary indication for referral remains in patients with levodopa-responsive PD, particularly those experiencing motor fluctuations, and those with symptoms not adequately controlled by medication. Satisfactory levodopa responsiveness has been widely accepted as criterion for patient selection.^19,20,21 While there is no strict age limit, it is important to consider that age at the time of surgery has been found to negatively impact the motor outcomes of STN-DBS.¹⁹ Cognitive decline, frequently seen in PD patients later in the disease, can limit the potential benefits of DBS surgery and, as such, the Mattis Dementia Rating Scale (MDRS) test is routinely performed as part of the evaluation process, with scores < 130 typically indicating unsuitable candidacy. In patients with postural instability, its benefits have also been found to be inconsistent.²²

Conditions that may elevate surgical risk, such as coagulopathy, uncontrolled hypertension and extensive cerebral atrophy, are considered contraindications for the surgery.¹⁸

DBS hardware

There are several DBS devices from different manufacturers, all of them comprise three fundamental components: intracranial electrode(s), a programmable implantable pulse generator (IPG) and an extension cable. The electrodes are made of thin coiled wires insulated with polyurethane and feature four to eight platinum iridium electrodes at their tips, designed for implantation in the target tissue. These electrodes are connected via an extension cable to a programmable IPG, typically implanted subcutaneously either below the clavicles or on occasion in the abdomen in patients with a low body mass index (BMI).

Surgery

DBS surgery comprises two stages and can be performed in one or two separate surgical procedures. The initial stage involves implantation of electrode(s) into the target nuclei, and the subsequent stage encompasses implantation of the implantable pulse generator (IPG) and internalisation of the leads.

The first stage of DBS surgery centres on mapping and accurately placing the electrodes into the intended target nuclei. The success of the procedure relies on the accuracy of electrode placement, with an error margin of < 2-3mm generally the aim for optimal clinical outcomes.^23,24 Various methods are used traditionally to refine targeting accuracy. These include the use of stereotaxy, electrophysiologic guidance through microelectrode recording (MER) and macrostimulation testing. Frame-based stereotactic neuronavigation has long been recognised as a standard for precise targeting of deep brain structures. The head frames that are commonly used are Cosman-Roberts-Well and Leksell frames.²⁵ A frameless system has been introduced in recent years, offering the advantages of superior patient comfort and shorter operating time.²⁶ MER is a neurophysiological technique commonly used as an adjunct in refining electrodeplacement.²⁷ It involves passing a microelectrode along its trajectory towards the target nuclei (STN or GPi) while recording neuronal discharges. Each specific target nucleus exhibits unique patterns in neuronal discharges and as such allow precise localisation of the intended nuclei targets.¹⁸ Recent advancements in intraoperative imaging-guided technology have however sparked controversy over the necessity of employing MER for precise targeting.^28,29,30 Not only does its application demand analysis by an experienced neurophysiologist, it also necessitates careful consideration regarding the choice of anaesthetic agent, as each agent alters MER to varying degrees. Macrostimulation testing is conducted intraoperatively on a conscious patient through the inserted DBS electrodes to verify symptom improvement. 

The integration of robot-assisted technology in neurosurgery has undergone substantial advancement since its first clinical application in 1988 and has transformative implications for DBS surgery. Robot-assisted DBS offers high level of precision, with electrode deviations reported to be ranging from 0.76mm to 1.6mm.³¹ It also has various advantages, including shorter operation time, easier trajectory adjustments, reliable reproducibility of arm position along a specified trajectory and elimination of human error.^32,33,34 Different robotic systems are available commercially, such as NeuroMate, ROSA and Renaissance.³⁵

Implantation techniques vary across different centres. At our institution, we utilise the ROSA ONE robot-assisted system in conjunction with Leksell Frame head fixation for electrode implantation. Prior to the DBS surgery, the patient first undergoes a pre-operative MRI, typically scheduled a week prior, performed under general anaesthesia (GA) to ensure minimal movement artefact. The acquired images are then registered into the ROSA ONE robot system. Following this, specific targets are identified and trajectories designed. The surgical procedure begins with affixing bone fiducial markers on to the patient’s skull after induction of general anaesthesia. Intraoperative stereotactic imaging is subsequently performed using the O-arm, the acquired images are then imported into ROSA software and merged with that of MRI. Following this, the ROSA ONE robot is securely affixed to the patient’s head through the use of Leksell headframe and the registration of fiducial markers is carried out. Scalp entry points are then demarcated with a pointer probe. A microdriver, equipped with a guiding tube is then affixed to the robot arm. After performing Burr hole and excision of dura, the robot arm then drives the microdriver along the predetermined trajectory to the target nuclei. A subsequent intraoperative scan is then performed to verify electrodelocation. Once inserted, the electrodes are secured and the wound closed.

The second stage of DBS surgery involves implanting the IPG and internalising the leads. In this phase, the electrodes that were previously implanted are connected to an extension cable, which is then tunnelled subcutaneously on the side of the neck before it is connected to the IPG, usually placed in the infraclavicular area. This can take place directly after the initial stage of the surgery or on a separate day. In our institution, we perform the second stage immediately following the first stage, sparing the patient from undergoing another general anaesthesia.

Anaesthesia

The anaesthetic approach for DBS surgery is closely linked to the chosen surgical techniques. The first part of the surgery (electrode implantation) can be done under general anaesthesia (GA), local anaesthesia (LA) or monitored anaesthesia care (MAC), while the second part of the surgery is typically conducted under GA.^18,36

Similar to other surgeries, routine non-invasive monitoring, in keeping with the Anaesthetists of Great Britain and Ireland (AAGBI) guideline, should be instituted. These include electrocardiogram (ECG), pulse oximetry and blood pressure. Invasive arterial line can aid in maintaining and monitoring haemodynamic stability during the prolonged procedure, particularly in patients with significant comorbidities. If ‘awake’ technique is utilised, urinary catheterisation is highly uncomfortable and is advisable to circumvent its use, consequently, careful fluid management intra-operatively is essential to avoid bladder distension.^18,36

Awake

The ‘awake’ technique is favoured if intraoperative MER/macrostimulation is anticipated and allows for precise mapping and unaltered MER.^18,36,37 It encompasses performing the surgery either with local anaesthesia only, or under monitored anaesthesia care with conscious sedation, with the latter being the preferred option. It has the advantages of minimising physiologic disruptions and expediting post-operative recovery in comparison to general anaesthesia.

The primary challenge for the anaesthetist in providing monitored anaesthesia care  in these surgeries lies in maintaining the sedation level where the patient’s comfort is optimised, while facilitating intraoperative neurophysiological mapping. When considering patients for ‘awake’ surgery, a strategy for airway rescue should be planned in advance. The use of a supraglottic airway device (SAD) can be particularly advantageous in such situations, as performing laryngoscopy on a patient with a stereotactic frame in place may prove difficult.^18,36 Anti-parkinsonian drugs will also need to be withheld and premedication used judiciously during the perioperative period to facilitate intraoperative neurological testing.¹⁸

Placement of a stereotactic frame in this technique can be aided by subcutaneous local anaesthesia infiltration, specifically targeting the pin sites. Alternatively, supra-orbital and greater occipital nerve blocks can also be employed, offering the advantage of superior comfort during the procedure.³⁸

The choice of anaesthetic agents depends mainly on their effect on MER/macrostimulation. All anaesthetic agents alter neuronal firing rates in basal ganglia by potentiating inhibitory action of GABA, and so can impact MER/macro-stimulation to varying degrees. The extent of this effect also differs among different diseases and target nuclei, potentially due to variations in their GABA input.³⁹ GPi nuclei receive a greater amount of GABA input compared to the STN nuclei, resulting in a higher susceptibility to suppression by anaesthetic agents.³⁶ To date, it is still unclear which anaesthetic agent allows the most effective MER.

The ideal agent for conscious sedation in DBS should have a rapid onset and offset, possess analgesic qualities, and minimally impact neurophysiological testing.³⁷ Dexmedetomidine has been the most popular agent since its advent and can be used to induce a state of ‘cooperative sedation’ crucial in DBS surgery.^40,41,42 It is a highly selective alpha-2-adrenoceptor agonist, primarily targeting locus caeruleus, a pivotal site within the central nervous system (CNS) regulating sleep, arousal and anxiety. It provides a dose-dependent sedation without the drawback of respiratory depression. Despite the tendency to decrease neuronal firing frequency like all other anaesthetic agents, studies have shown that a low dose (up to 0.6mcg/kg/hour) does not significantly alter subcortical activity and, as such, confers its superiority in providing sedation while facilitating neurophysiological testing.⁴¹

Benzodiazepines are generally avoided both pre-operatively and intra-operatively due to their direct GABA action with the potential to abolish MER during the mapping phase. They can also induce dyskinesia in the perioperative period.⁴³ Propofol, although being widely used for sedation, comes with its share of drawbacks within the context of sedation in DBS. Studies have shown that propofol can diminish MER and induce dyskinesia.^44,45 If used as target-controlled infusion (TCI), it is also important to note that the pharmacokinetic profile of propofol in patients with PD differs from that of the general population, and as such, its effect may not align with that of the intended target.⁴⁶

Remifentanil is another widely utilised drug, often administered in conjunction with propofol to facilitate conscious sedation. It acts as an μ-receptor agonist, offering the unique properties of ultra-short duration of action along with analgesic properties. The extent of its impact on MER remains less well understood, with certain data indicating its potential to suppress tremors, which may have implications for intraoperative neurocognitive testing.^37,47

Asleep

The premise of ‘asleep’ technique lies in a reduced emphasis on neurophysiological validation in ways of MER/macrostimulation. With the advancement of intra-operative imaging modalities, the evolution of DBS surgery has seen a shift in recent years from ‘awake’ technique to an increasing reliance on general anaesthesia. Multiple studies have sought to compare the advantages of general anaesthesia versus local anaesthesia in the context of DBS and have yielded conflicting results.^48,49,50

However, meta-analysis has shown comparable clinical outcomes in DBS surgery between general anaesthesia and local anaesthesia, encompassing symptoms improvement and the incidence of adverse events.⁵¹ Notably, despite these findings, level 1 evidence is still lacking to date concerning long-term outcome. The ‘asleep’ technique is often the technique of choice when robot assistance is used, or when neurophysiological validation is not of consideration. While still allowing MER, macrostimulation cannot be conducted under general anaesthesia, which prevents patients from reporting subjective sensations like paraesthesia resulting from the stimulation of adjacent structures, such as the internal capsule and medial lemniscus.³⁶ It serves as a useful alternative to the specific cohort of patients for whom awake surgery is impractical, such as those with anxiety issues or severe dyskinesia and dystonia.^18,36

The ‘asleep’ approach has several advantages, including enhanced patient comfort, safety, and an expansion of patient eligibility by alleviating the need of prolonged periods of lying flat. In instances where PD is the indication, anti-parkinsonian drugs also need not be discontinued in the peri-operative period.

General anaesthesia (GA) is typically induced with a bolus of short-acting opioid and propofol. Patients are commonly paralysed and intubated with a reinforced endotracheal tube (ETT), followed by the application of the head frame. A nasogastric tube is inserted to allow the administration of anti-parkinsonian drugs intraoperatively. The maintenance of anaesthesia can be achieved through either total intravenous anaesthesia (TIVA) or inhalational agents. In cases where microelectrode recording (MER) is employed, the concentration of anaesthetic agent is typically titrated down 15-30 minutes prior to MER to mitigate its impact.³⁷ This approach reflects the standard practices employed in our institution. It is worth noting that we do not incorporate MER into our procedures at Beaumont Hospital.

Conclusion

The establishment of the national deep brain stimulation service in Ireland marks a critical milestone in providing care for patients with complex neurological disorders. Despite the challenges associated with patient selection and peri-operative planning, DBS surgery continues to demonstrate remarkable benefits and has a transformative impact on those with movement disorders refractory to conventional therapies.

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