Conference Lectures

ANAESTHESIA FOR DEEP BRAIN STIMULATION

M. Radhakrishnan M.D., D.M.
Additional professor
Department of Neuroanaesthesia
NIMHANS, Bangalore, India.

 

Introduction:
Deep brain stimulation (DBS) is a minimally invasive, functional, neurosurgical procedure in which stimulating electrodes are placed into the target nuclei, usually bilaterally, for symptom relief and to improve the quality of life in various neurological disorders. It is most commonly done for movement disorders, but there are other emerging conditions as well (table 1).
Motor functions are coordinated by nuclei situated in the basal ganglia and in the cerebellum and fine-tuned by cerebral cortex, brain stem and spinal cord (figure 1). Damage to basal ganglia nuclei can result in movement disorders. In Parkinson’s disease (PD), there is damage to the substantianigra and imbalance in the neurotransmitters, especially dopamine and acetylcholine.
Assessment:
Parkinson’s disease is clinically assessed by Unified Parkinson’s disease rating scale (UPDRS) measurement [1]. The Hoehn and Yahr scale of staging Parkinson’s disease is incorporated in to this UPDRS.
Indications:
Table1 listsall the established and potential indications for DBS and corresponding target nuclei for DBS placement in various neuro-psychiatric disorders [2].

 

 

Table 1: Clinical conditions for deep brain stimulator placement.

Indications		Target locations
Established	Idiopathic Parkinson’s disease   (PD)	Subthalamic nucleus (STN), Globus pallidusinternus (GPi)
	Idiopathic essential tremors	Ventral Intermediate nucleus of thalamus(VIN), posterior subthalamic area
	Dystonia	GPi
Emerging	Obsessive compulsive disorder	Right nucleus accumbens, STN, ventral capsule (VC), ventral striatum (VS)
	Chronic pain	Periacqueductal gray, periventricular gray, thalamus
	Major depression	Subgenual cingulate cortex, nucleus accumbens, VC/VS
	Refractory epilepsy	Multiple (anterior nucleus of thalamus)
Investigational	Other tremors	VIN, STN, nuclei of tegmentipedunculopontine
	Alzheimer’s disease	Hypothalamus
	Minimally conscious/ vegetative state	Central thalamus, mesencephalic reticular formation

DBS is attempted when medical management is no longer effective or is associated with side effects. In PD, long term dopamine therapy results in dyskinesia, fluctuating on-off symptoms and ineffective control of motor symptoms. For DBS to be effective in PD there should be at least 30% improvement in the UPDRS following supratherapeutic doses of levodopa.
Surgical technique:
Initially, patient undergoes magnetic resonance imaging (MRI) for target site localisation and referencing to external coordinates (frame). Even though the target nucleus is identified with MRI, for optimal placement of stimulator leads, additional techniques like micro electro recordings (MERs), intraoperative MRI, intraoperative duplex cranial ultrasound and C-arm are required. MERs assess spontaneous background activity and spike activity of deep nuclei. Each target nucleus has specific pattern of activity and firing rate (ex: GPi: 60-80Hz).
In the operation theatre, patient’s head is fixed to the stereotactic frame. A burr hole is made on one side. Microelectrodes are placed close to the target nucleus and cellular recordings are made. The electrodes are moved down either manually or by motor device to identify the best locationfor the lead placement, based on the firing pattern of the cells. After this, macro electrode stimulation is performed  to look for symptom relief(tremor) and associated side effects due to stimulation of the neighbouring neural structures (ex: visual disturbances, limb weakness). From the time of micro electrode placement till macro stimulation, the patient needs to remain awake for clinical examination. After identifying the location, stimulating electrode is placed and the procedure is repeated on the other side. After lead placement on both sides, a pulse generator is placed in the chest by making a subcutaneous pouchin the anterior aspect of the chest and the leads are tunnelled through the neck and connected to the pulse generator. This part of the procedure is done under general anaesthesia (GA) [3].
Anaesthetic interactions:
Anesthetics affect both MER and macrostimulation. However, the effects are different for different anaesthetic agents and the same drug acts differently in different nuclei. Propofol has been used successfully at target controlled infusion of 0.8-2 microgram/ml without interfering with the recordings [4, 5]. GPi neurons have abundant GABA receptors and are susceptible to anesthetic agents as compared to other nuclei (ex: STN).
Mechanisms of DBS action:
The nucleus in the basal ganglia normally fires at less than 100Hz (40-80 Hz). In DBS, the pulse generator fires at more than 100Hz (135-185Hz). When this happens in the target nuclei, there is disruption in the circuit (“noise”) controlling the body movements. This helps in the symptom relief (tremor, rigidity). The other mechanisms proposed are inhibition/stimulation of gamma amino butyric acid (GABA) responsive cells and evoked release of dopamine.
Contra-indications*:

1. Anticoagulation therapy (increased chance of intracranial bleed)
2. Uncontrolled hypertension (increased chance of intracranial bleed)
3. Ongoing electroconvulsive therapy
4. Parkinson’s plus disease and drug induced PD

* need for future MRI is not a contraindication for DBS procedure [6].
Figure 1: Extrapyramidal system nuclei. +,- represent positive and negative control on the nuclei respectively. Circle represents the neurotransmitter involved in the particular circuit.

Medications used in PD:

Drug class	Drugs	Side effects
Dopamine therapy	Levodopa, carbidopa	Orthostatic hypotension
Centrally acting dopamine agonists	Bromocriptine, pergolide	Mental changes, Orthostatic hypotension
Anticholinergics	Trihexyphenydyl	Dry mouth, urinary retention
Antiviral	Amantadine	Skin flushing, edema, confusion
MAO-B inhibitors	Selegiline	Dizziness, nausea, insomnia, abnormal glucose metabolism

Perioperative concerns:

1. Patient related – comorbidities, PD induced organ system changes
2. Prolonged surgery (duration becoming shorter with surgeries performed under GA)
3. Need for awake and cooperative patients
4. Influence of anesthetic agents on MER
5. Exaggeration of symptoms during drug withdrawal
6. Intraoperative complications (ex: airway related, intracranial bleed, seizures)

PD associated systemic changes:
1. Rigidity involving the pharyngeal, laryngeal muscles can result in breathing difficulty, increased risk for aspiration pneumonia, stridor following extubation (drug withdrawal phase).
2. Rigidity involving the respiratory muscles might impair breathing. This can theoretically get aggravated with opioid usage.
3. Cardiovascular changes include hypotension which is orthostatic in nature (causes - levodopa, autonomic dysfunction, hypovolumia), arrhythmias.
4. Weight loss and poor nutrition – Reduced requirements of anaesthetic agents.
Preoperative evaluation:
A thorough preoperative evaluation is required as these patients are usually elderly with associated co-morbidities. Concerns listed above must be looked for and assessed with appropriate clinical examinations and lab tests. Since these procedures are elective, patients’ medical condition should be optimised prior to surgery. The long duration of surgery and the need for awake state during the procedure must be explained to the patient. The need for stopping the anti-Parkinson drug should be explained.
Anesthetic technique:
Patient co-operation is very essential if awake technique is planned. The procedure is long lasting; patient has to remain immobile in the supine/semi-sitting position. Patients with anxiety disorder, claustrophobia, low tolerance to pain are not ideal candidates for this awake procedure.
Airway must be carefully assessed prior to starting the procedure as the patient’s head will be rigidly fixed to the frame limiting the access to the airway. Extra care and backup plan should be available while managing patients with difficult airway. In this surgical procedure, brain relaxation is not a concern.
Premedication like benzodiazepines is usually avoided as it causes depression of MER. Patient’s routine anti-PD are withheld on the morning of surgery to facilitate MER. Patients should be explained of the possibility of exaggeration of symptoms to reduce anxiety during the surgical procedure. Standard ASA monitoring is applied to the patient (including EtCO2). Invasive arterial line is optional and is decided upon by patient’s co-morbid conditions. Foley’s catheter for urine drainage is usually required as the surgery is prolonged.Local anaesthetic infiltration, pin site infiltration and scalp block provide long lasting analgesia.

Drapes should leave the face free for airway access; monitoring and ventilation.Proper patient positioning with support to neck, legs and hands must be ensured. Anesthetic technique can be asleep-awake-asleep (AAA)/monitored anaesthesia care (MAC) /awake. For MAC, the drug choices include propofol, dexmedetomidine, fentanyl and remifentanyl (not available in India) either as bolus dose or as infusion. It is better to stop the infusion some time before the recording of MER. MER suppression with propofol is greater as compared to dexmedetomidine. If propofol is used for sedation, it should be stopped at least15-20min prior to starting the MER. Dexmedetomidine can be continued,preferably at low doses (0.05-0.1µgm/kg/hr) during MER [7]. Caution is required while using this drug as it has been shown to supress abnormal movements in dystonic patients [8].Dexmedetomidine has been successfully used in children with dystonia for DBS placement. Most common side effects include bradycardia and hypotension. Caution is required while using in elderly patients who are already on beta blockers.For AAA technique, during the initial phases of surgery, after induction, laryngeal mask airway (LMA) is inserted. During the MER, anesthesia is lightened and LMA removed. Once the recording is done, LMA is inserted. Any straining during LMA removal can cause brain bulge or scalp injury as patient’s head is fixed to stereotactic frame. AAA technique can also be practiced without airway intervention using titrated propofol and remifentanyl infusion. There are reports in which anaesthetists have used endotracheal tube for the procedure. For the reinsertion, fiberoptic bronchoscopy was used. Recently there are published reports on patients undergoing DBS under full GA with endotracheal intubation, especially if sub-thalamic nucleus is the target nuclei[9]. GPi MERs are susceptible to volatile agents and MER from STN are more robust compared to other target areas. 

Anti PD drugs are usually stopped before the procedure to facilitate MER, but can be associated with exaggeration of tremors. Recently apomorphine (injectable opioid) with dopaminergic activity has become available to control the symptoms (not available in India).
For the pulse generator placement, general anaesthesia is administered either through LMA or endotracheal tube.
Complications:
Haemorrhage- risk factors include number of attempts taken to place MER electrodes and macro electrodes and transventricular lead trajectories.
Seizures – occurs when patient suffers from intracerebral bleed, age >60years,
Postoperative nausea and vomiting
Cardiovascular
Hypotension
Drug induced – Bromocriptine, Pergolide, Other anti-Hypertensives
Autonomic failure
Hypertension – more commonly seen in MAC than in GA. It is a risk factor for ICH. Dexmedetomidine reduces the incidence of hypertension.
Bradycardia
Arrhythmia
Venous air embolism (semisitting position)
Symptoms include Cough, anxiety, chest discomfort. It is better to use precordial Doppler during the semi-sitting position.
Rare complications:
Stroke
Tension pneumocephalus
Postoperative behavioural and cognitive problems.Haloperidol is contraindicated in these patients (because of its anti -dopaminergic activity), selective blockers like clozapine and quetiapine can be used to treat this condition.
Postoperative memory dysfunction has been described in patients undergoing DBS placement under general anaesthesia [10].
Electrical interferences
MER can be severely disrupted by warmers, infusion pumps, monitors, pneumatic Compression devices and other electric devices. These machines should be turned off while doing the MER.
Postoperative akinetic-rigidity state
This is seen in patients who come for replacement of batteries. If the pulse generators are not activated immediately, patients go in for akinetic unresponsive state. These patients do not respond to dopamine therapy [11].
Conclusion:
The indication for deep brain stimulation is increasing with increasing knowledge of circuitry function of deep nuclei and advancement in technology and approach. With newer modalities like intraoperative MRI, more patients are undergoing this procedure under GA. For an awake procedure, various anaesthetic techniques are available with or without airway intervention. Patients’ systemic problems should be properly evaluated and optimised before subjecting them to surgery.
References:

1. Claudia R, Johan M, Margarethe SA, et al. Systematic evaluation of rating scales for impairment and disability in Parkinson's disease. Movement Disorders 2002; 17: 867–76.
2. Erickson KM, Cole DJ. Anesthetic considerations for awake craniotomy for epilepsy and functional neurosurgery. Brambrink AM, Kirsch JR Ed. In Anesthesiol Clinics. 2012; 30: 241-68.
3. Venkatraghavan L, Manninen P. Anesthesia for deep brain stimulation. CurrOpinAnesthesiol 2011;24: 495-9.
4. Raz A, Eimerl D, Zaidel A, et al. Propofol decreases neuronal population spiking activity in the subthalamic nucleus of Parkinsonian patients.AnesthAnalg 2010; 111: 1285-1289.
5. Maltete D, Navarro S, Welter ML, et al. Subthalamic stimulation in Parkinson disease: with or withoutanesthesia. Arch neurol 2004; 61: 390-2.
6. Chabbra V, Sung E, Mewes K, et al. Safety of magnetic resonance imaging of deep brain stimulator systems: a serial imaging and clinical retrospective study. J Neurosurg 2010; 112:497-502.
7. Sebeo, J., S. G. Deiner, et al. Anesthesia for pediatric deep brain stimulation. Anesthesiol Res Pract 2010.doi:10.1155/2010/401419.
8. Rao MB, Radhakrishnan M. Dexmedetomidine for a patient with Hallervorden-Spatz syndrome during magnetic resonance imaging: a case report. J Anesth. 2013;27:963-4.
9. Harries A, Kausar J, Roberts SAG, et al. Deep brain stimulation of the sub-thalamic nucleus for advanced Parkinson disease using general anesthesia: long-term results. J Neurosurg 2012; 116:107–113.
10. Tsai ST, Chen SY. Letter to the Editor: Deep brain stimulation and general anesthesia. J Neurosurg 2012; 117: 1207-8.
11. Dagtekin, O., T. Berlet, etal.Anesthesia and deep brain stimulation: postoperative akinetic state after replacement of impulse generators. AnesthAnalg 2006; 103: 784.