Movement disorder surgery Part I: historical background and principle of surgery

Abstract

Learning objectivesBy reading this article you should be able to:•Describe the five key stages in the evolution of movement disorder surgery.•Explain the selection criteria for patients with Parkinson's disease, essential tremor, and dystonia.•Discuss the different approaches to deep brain stimulation (DBS) surgery, such as frame-based or frameless systems, direct or indirect targeting.•Detail the complications that can arise from DBS surgery.Key points•DBS is a safe and effective treatment for Parkinson's disease, essential tremor, and dystonia.•Multidisciplinary team involvement is a prerequisite through all stages of DBS surgery.•Appropriate selection of patients, detailed imaging, accurate anatomical targeting, and electrophysiological verification are critical for a successful outcome.•DBS surgery has well-recognised complications including intracranial haemorrhage, hardware, and stimulation-related problems. By reading this article you should be able to:•Describe the five key stages in the evolution of movement disorder surgery.•Explain the selection criteria for patients with Parkinson's disease, essential tremor, and dystonia.•Discuss the different approaches to deep brain stimulation (DBS) surgery, such as frame-based or frameless systems, direct or indirect targeting.•Detail the complications that can arise from DBS surgery. •DBS is a safe and effective treatment for Parkinson's disease, essential tremor, and dystonia.•Multidisciplinary team involvement is a prerequisite through all stages of DBS surgery.•Appropriate selection of patients, detailed imaging, accurate anatomical targeting, and electrophysiological verification are critical for a successful outcome.•DBS surgery has well-recognised complications including intracranial haemorrhage, hardware, and stimulation-related problems. The management of patients with refractory movement disorders is challenging. This review focuses on the evolution of surgery as a treatment option for movement disorders, patient selection and principles of surgical treatment. The evolution of movement disorder surgery (MDS) can be described in five key stages: the prestereotactic era; the early stereotactic era; the latent period after the introduction of levodopa; the resurgence of stereotactic ablative surgery; and the modern era of implanted deep brain stimulators.1Gildenberg P.L. The history of surgery for movement disorders.Neurosurg Clin N Am. 1998; 9: 283-294Abstract Full Text PDF PubMed Google Scholar Between the late 1900s to the 1930s, with rudimentary understanding of the pathogenesis and neuroanatomical basis for motor control, various experimental surgical treatments for movement disorders were carried out, with mixed results. The early success of Foerster in 1911, who performed dorsal rhizotomy to treat spasticity in children, was not reproduced with other procedures targeting the peripheral nervous system such as sympathetic ramisection, ganglionectomies, and cordotomies.2Foerster O.H. Resection of the posterior spinal nerve roots in the treatment of gastric crises and spastic paralysis.Proc R Soc Med. 1911; 4: 226-246PubMed Google Scholar The belief that treatment of movement disorders required interruption of pathological signals in the pyramidal tract led to the use of primary cortex ablative surgery, with the first reported cortical ablation for the treatment of Parkinson's disease (PD) tremor in 1937 by Bucy and Case.3Bucy P.C. Case J.T. Tremor: physiological mechanism and abolition by surgical means.Arch Neurol Psychiatr. 1939; 41: 721-746Crossref Scopus (59) Google Scholar Despite producing symptomatic improvement, corticectomy was ultimately abandoned in the 1950s as a result of inconsistent postoperative outcomes, high morbidity and mortality. Basal ganglia and extrapyramidal pathways were considered poor surgical targets, because of their importance in maintaining consciousness, until Meyers demonstrated that surgery to targets within the basal ganglia can improve symptoms of tremor and rigidity without impairing consciousness.4Meyers R. The modification of alternating tremors, rigidity and festination by surgery of the basal ganglia.Proc Assoc Nerv Ment Dis. 1940; 21: 602-665Google Scholar In 1952, Cooper inadvertently injured the anterior choroidal artery of a patient with PD during a pedunculotomy.5Cooper I.S. Ligation of the anterior choroidal artery for involuntary movements; parkinsonism.Psychiatr Q. 1953; 27: 317-319Crossref PubMed Scopus (107) Google Scholar The patient emerged from anaesthesia with resolution of his tremor and rigidity, and with no motor deficit despite infarction of the globus pallidus.5Cooper I.S. Ligation of the anterior choroidal artery for involuntary movements; parkinsonism.Psychiatr Q. 1953; 27: 317-319Crossref PubMed Scopus (107) Google Scholar This serendipitous discovery, along with the advent of human stereotactic surgery using a modified Horsley-Clarke frame (which reduced operative mortality to 2%), resulted in the development of exploratory procedures on various subcortical targets.6Spiegel E.A. Wycis H.T. Marks M. et al.Stereotaxic apparatus for operations on the human brain.Science. 1947; 106: 349-350Crossref PubMed Scopus (571) Google Scholar In the 1960s, the introduction and success of levodopa resulted in a dramatic decline in the use of surgery for movement disorders. However, the realisation that long-term levodopa therapy is associated with troublesome adverse effects (motor fluctuations and dyskinesia), along with an improved understanding of functional neuroanatomy, resulted in a resurgence of MDS. Further refinements in surgical technique and treatment targets to include the ventral intermedius (VIM) nucleus of the thalamus resulted in patients being referred for treatment of multiple sclerosis and essential tremor (ET) and for the symptoms of PD. These ablative procedures were limited to those with unilateral symptoms as bilateral ablation was associated with disabling psychiatric and corticobulbar adverse effects. Up to this point, MDS involved destruction of tissue in the target area. Electrical brain stimulation had long been used to predict the effectiveness of the intended surgical target for lesioning. Chronic deep brain stimulation (DBS) was first reported as a therapeutic intervention for movement disorders in the 1980s.7Benabid A.L. Pollak P. Louveau A. et al.Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson’s disease.Appl Neurophysiol. 1987; 50: 344-346PubMed Google Scholar DBS has since gained popularity because of excellent clinical efficacy, its reversibility, and adjustability. DBS is now a well-established treatment for movement disorders such as PD, ET, and dystonia. This article focuses primarily on DBS surgery. Other techniques such as thermal ablation, magnetic resonance-focused ultrasound, and gamma knife lesioning are not discussed here. Neurorestorative procedures for PD, such as gene therapy, fetal and stem cell transplantation, are promising but are currently experimental. Successful surgery depends on appropriate selection of patients, detailed preoperative evaluation, choice of anatomical target, accurate target localisation, and expert neurosurgical skills. These factors rely on the coordination of the multidisciplinary team of neurosurgeon, neuroanaesthetist, neurologist, neurophysiologist, neuroradiologist, neuropsychologist, and specialist nurses. It is crucial that the patient and family members are involved in the process. The development of DBS was based on observed similar therapeutic effects of high-frequency stimulation and lesions in the same area. The exact underlying mechanism of action of DBS remains uncertain, but it is likely to result from both stimulatory and inhibitory effects on neural elements that affect the generation and propagation of electrical signals through the cortico-striatal-pallidal-thalamic-cortical (CSPTC) network (Fig. 1). DBS also results in changes to glutamate and γ-aminobutyric acid (GABA) pathways within the network.8Chiken S. Nambu A. Mechanism of deep brain stimulation: inhibition, excitation, or disruption?.Neuroscientist. 2016; 22: 313-322Crossref PubMed Scopus (168) Google Scholar These mechanisms disrupt abnormal signals within the CSPTC network that are present in pathological conditions such as PD. Chronic DBS has also been shown to affect synaptic and neural plasticity, resulting in long-term neuronal reorganisation.9Herrington T.M. Cheng J.J. Eskandar E.N. Mechanisms of deep brain stimulation.J Neurophysiol. 2016; 115: 19-38Crossref PubMed Scopus (186) Google Scholar Advances in functional brain imaging and experimental research on animal models have advanced our understanding of the neural circuitry of movement disorders. The CSPTC circuit comprises parallel, segregated loops for limbic, associative, oculomotor, and skeletomotor function. In the CSPTC motor loop, excitatory signals from cortical areas are received by striatal input structures: the caudate and the putamen. The signal is then passed to the output structures: the globus pallidus interna (GPi) and substantia nigra pars reticulate (SNr) via a direct, monosynaptic pathway. An indirect pathway receives input from the striatum and passes via the globus pallidus externa and subthalamic nucleus (STN) before terminating at the GPi and SNr. The GPi and SNr send inhibitory signals to the cortex through the thalamus, completing the circuit (Fig. 1). Degeneration of dopaminergic neurones in the substantia nigra pars compacta (SNc) and consequent dopamine deficiency in pathways receiving input from the SNc result in the manifestation of PD. An understanding of CSPTC motor circuits allows the identification of potential surgical targets for treatment of movement disorders. Both STN and GPi are established targets for treatment of PD symptoms (Fig. 2A and D). VIM stimulation is effective for ET of the upper limb, while DBS for dystonia targets the GPi. Appropriate selection of patients is a major factor in predicting successful outcome in DBS surgery, requiring input from a multidisciplinary team. More than 30% of cases where DBS fails can be attributed to inappropriate selection of patients.10Okun M.S. Tagliati M. Pourfar M. et al.Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers.Arch Neurol. 2005; 62: 1250-1255Crossref PubMed Scopus (295) Google Scholar The patient (and family) should be counselled on the risks and benefits of the procedure, the stages involved, and the requirement for long-term follow-up. The patient should be in good overall health with medical comorbidities optimised. As part of preoperative assessment, patients should also undergo neuropsychological evaluation both to assess their suitability for surgery and as an important baseline assessment. As patients with underlying cognitive impairment are at risk of further decline after surgery, severe preoperative cognitive impairment is a contraindication for surgery. Patients with mild cognitive impairment should be reviewed on a case-by-case basis. Surgical intervention in patients suffering from psychiatric conditions such as dementia, psychosis, and refractory depression is not recommended. DBS surgery can be carefully considered for patients with PD refractory to pharmacological treatment. The diagnosis and pharmacological management of PD have been reviewed elsewhere.11Chambers D.J. Sebastian J. Ahearn D.J. Parkinson’s disease.BJA Educ. 2017; 17: 145-149Abstract Full Text Full Text PDF Scopus (6) Google Scholar Although there is currently no robust evidence-based guideline to help determine suitability for DBS surgery, expert consensus recommendations can guide decision-making (Box 1).12Bronstein J.M. Tagliati M. Alterman R.L. et al.Deep brain stimulation for Parkinson disease an expert consensus and review of key issues.Arch Neurol. 2011; 68: 165-171Crossref PubMed Scopus (588) Google ScholarBox 1Summary of consensus statement on criteria for DBS surgery in patients with PD. ∗UPDRS III, Unified Parkinson Disease Rating Scale III.Tabled 1•Advanced idiopathic PD•Disability arising from motor fluctuations, dyskinesias or tremor despite optimal pharmacological therapy•Excellent response to formal levodopa challenge (at least 30% improvement in UPDRS III∗ score)•No or very mild cognitive impairment•No or well controlled psychiatric disease Open table in a new tab Tabled 1•Advanced idiopathic PD•Disability arising from motor fluctuations, dyskinesias or tremor despite optimal pharmacological therapy•Excellent response to formal levodopa challenge (at least 30% improvement in UPDRS III∗ score)•No or very mild cognitive impairment•No or well controlled psychiatric disease Open table in a new tab DBS benefits patients with a diagnosis of idiopathic PD. Patients with atypical or secondary Parkinsonism have less favourable outcomes, therefore surgical intervention is not recommended. Successful outcome is also dependent on the patient's response to levodopa. The exception to this rule is applied to levodopa-resistant tremor. Age alone should not exclude patients from surgery if they fulfil other selection criteria. It is important that these recommendations are not rigidly applied but rather used as an additional tool to aid the selection process. Subjective considerations such as impact on quality of life should be considered when determining candidacy for surgery. ET is defined as an isolated tremor syndrome affecting the upper limbs for at least 3 yrs, with or without tremor in other areas, in the absence of other neurological signs. Misdiagnosis is common because of overlap of clinical features with PD and other tremor disorders. A dopamine transporter scan is often useful to differentiate tremor-dominant PD from ET. The outcome of surgery depends on the type and clinical distribution of tremor. Patients with resting or distal postural tremor have a more favourable outcome after surgery than those with proximal postural or intention tremor.13Deuschl G. Bain P. Deep brain stimulation for tremor [correction of trauma]: patient selection and evaluation.Mov Disord. 2002; 17: S102-S111Crossref PubMed Scopus (68) Google Scholar DBS implantation can be unilateral or bilateral depending on functional improvement after unilateral treatment, usually of the dominant hand. Patients with disabling ET that impairs day-to-day function despite optimal pharmacological treatment (e.g. propranolol, primidone) should be considered for DBS. Dystonia is a heterogeneous disorder characterised by ‘sustained or intermittent muscle contraction causing abnormal, often repetitive movements, postures or both’. Dystonic movements are typically patterned, twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activity.14Albanese A. Bhatia K. Bressman S.B. et al.Phenomenology and classification of dystonia: a consensus update.Mov Disord. 2013; 28: 863-873Crossref PubMed Scopus (1171) Google Scholar Primary or idiopathic dystonia has no identifiable cause for the patient's symptoms, although a small group may have DYT-1 or DYT-6 gene mutations. Secondary dystonia is associated with an identifiable cause such as structural brain injury, metabolic disorders (e.g. Wilson's disease, mitochondrial disorders), and other heredodegenerative disorders (e.g. Huntingdon's disease, spinocerebellar degeneration). Patients should be considered for surgical treatment if they have failed to improve with pharmacological treatment (anticholinergic, antiepileptic, benzodiazepine, or baclofen) and botulinum toxin injections. Patients with primary/idiopathic, generalised dystonia benefit most from DBS.15Ostrem J.L. Starr P.A. Treatment of dystonia with deep brain stimulation.Neurotherapeutics. 2008; 5: 320-330Crossref PubMed Scopus (152) Google Scholar DBS for secondary dystonia, especially in patients with structural brain abnormality, is less effective with the exception of tardive dystonia. DBS surgery can be undertaken with the patient awake, partially awake, or under general anaesthetic. The choice of anaesthetic technique will be discussed in part 2 of this article. The basic components of DBS surgery include preoperative imaging, stereotactic anatomical targeting, burr hole placement, intraoperative physiological target verification, and lead implantation followed by implantation of a power source (i.e. an implantable pulse generator, IPG). Currently there is no standardised approach to DBS surgery because few comparative data are available. The approach varies depending on institutional preference, training and logistics. Ventriculography was the original imaging modality of choice. It reliably identifies the anterior commissure (AC) and the posterior commissure (PC), which are used as reference points during indirect targeting. This is an invasive procedure requiring infusion of air or contrast medium into the ventricular system. Ventriculography has been superseded by modern non-invasive imaging modalities such MRI and CT. MRI is the preferred imaging modality for target selection and trajectory planning because of its superior tissue differentiation. The resolution allows for direct visualisation of deep brain nuclei in multiple planes (Fig. 2A). However, MRI images are prone to distortion. CT images, by contrast, have limited resolution but are free from distortion and can therefore provide an accurate localisation of fiducial markers. The two imaging modalities can be combined to take advantage of each modality's strengths, although this introduces the possibility of registration errors. Imaging within DBS surgery remains controversial, with no clear international consensus. Typically, an MRI is obtained before surgery and uploaded to the stereotactic device software. On the day of surgery, the stereotactic frame is mounted onto the patient's head and CT images are obtained during surgery. In centres with interventional MRI theatre suites, target selection and trajectory planning occur on the day of surgery. A mobile sterile field allows for movement of the patient in and out of the scanner. Live images guide the neurosurgeon the trajectory towards the selected target. No preoperative imaging, preliminary target selection, trajectory planning, or stereotactic head frame is required. Accuracy of anatomical target localisation is critical to the success of DBS. A combination of methods may be used to improve the accuracy of electrode placement, including stereotactic imaging, intraoperative microelectrode recording (MER) mapping of the target structure and clinical assessment of the awake patient. Stereotactic imaging can be achieved either through a frame-based or a frameless system. Both systems have fiducial markers visible on CT or MRI images. These markers are used to produce a three-dimensional coordinate map of the brain. The frame-based approach is well established and is considered the ‘gold standard’. A variety of head frames are available such as the Leksell frame, the Cosman-Roberts-Wells frame, and the Riechert-Mundinger frame. Fiducial markers are located on the frame and act as reference points on the imaging obtained. These coordinates are uploaded to the stereotactic software system, which is then used to locate and plan the target entry point and trajectory. The frameless system requires fiducial markers to be affixed onto the patient's skull. This can be done before the day of surgery allowing the surgical team to plan the surgical trajectory to the anatomical target of interest ahead of time. Alternatively, surface anatomy features or the contours of the scalp and face can be used to register the images. Although the frameless system has been reported to be more advantageous in terms of patient comfort and reduced operating time,16Holloway K.L. Geade S.E. Starr P.A. et al.Frameless stereotaxy using bone fiducial markers fro deep brain stimulation.J Neurosurg. 2005; 103: 404-413Crossref PubMed Scopus (154) Google Scholar the frame-based approach is generally accepted to be more accurate. There are two types of targeting techniques: direct or indirect targeting. Direct targeting is where the point of entry and the trajectory planning is based solely on the patient's imaging. This requires high image resolution for the deep brain nuclei to be identified and ideally the borders delineated. Borders of the STN and GPi can be identified with 3 Tesla MRI, but the VIM is difficult to see on conventionally available MRI systems. Specific sequences can be used to highlight target nuclei. T2 and susceptibility weighted images will accentuate the STN, while proton density sequences can delineate the GPi. Indirect targeting uses anatomical brain atlases (e.g. the Schaltenbrand and Wahren atlas and the Talairach atlas) based on dissected brains to identify deep brain structures.17Schaltenbrand G. Wahren W. Atlas for stereotaxy of the human brain. Thieme Medical Publishers, Stuttgart1977: 41-47Google Scholar,18Talairach J. Tournoux P. Co-plannar stereotactic atlas of the human brain. Thieme Verlag, Stuttgart1988: 5-9Google Scholar The atlases use a set distance from the AC, PC, and midcommissural point identified by stereotactic imaging to approximate the coordinates of the target nuclei. It is worth noting that there is significant variability in the size, shape, and location of basal ganglia and thalamic targets between patients, making reliance solely on indirect targeting unreliable. Displacement of the brain within the cranial vault relative to preoperative imaging may arise from several causes, including CSF loss, pneumocephalus, and the mechanical process of lead insertion resulting in brain deformation. Such brain shift can cause deviation of the intended trajectory and target, resulting in suboptimal lead placement and increased risk of damage to adjacent structures. A few millimetres of displacement can adversely affect the outcome of DBS surgery.19Rezai A.R. Machado A.G. Deogaonkar M. et al.Surgery for movement disorders.Neurosurg. 2008; 62: 809-838Crossref PubMed Scopus (2) Google Scholar Intraoperative electrophysiological verification can overcome this phenomenon. There are several electrophysiological techniques that can be used including MER, intraoperative stimulation, and impedance measurements. More than 95% of DBS centres in North America use MER to assist lead placement confirmation.20Ondo W.G. Bronte-Stewart H. The North American survey of placement and adjustment strategies for deep brain stimulation.Stereotact Funct Neurosurg. 2005; 83: 142-147Crossref PubMed Scopus (59) Google Scholar The MER technique varies between centres. Patients are generally kept awake to avoid the suppressant effects of anaesthesia on neuronal activity. The recording can register neuronal activity of a single neurone or multiple units, and can be from a single penetration tract or multiple microelectrodes. The STN, GPi, and VIM have distinctive electrophysiological signatures that allow accurate identification using MER. MER is no longer considered a gold standard because of the increased risk of haematoma, and is not standard practice in the UK. After physiological confirmation, the microelectrode is removed, and the DBS lead is passed via the same tract to the target depth. Fluoroscopy can be used to monitor this process. The tip of the DBS brain lead has a number of discrete contacts allowing the volume of brain tissue activated by the lead to be varied along the long axis of the lead. Directionality of stimulation is achieved through separation of contacts into separate segments. A standard DBS lead has up to eight individual contacts, allowing fine-tuning of stimulation and reduction in adverse effects. Once the lead is implanted, intraoperative stimulation may be carried out to assess the clinical improvement and adverse effect threshold. The stimulation parameters will be similar to that used for chronic stimulation and the patient should demonstrate improvement of symptoms. Alternatively, the lead position is checked by post-implantation imaging if surgery is carried out solely under general anaesthesia. The DBS lead is secured to the cranium and the distal tip of the lead attached to an extension wire, which is tunnelled subcutaneously to the parietal region. Most centres confirm DBS lead placement with postoperative control imaging, preferably using MRI (Fig. 2B and C).20Ondo W.G. Bronte-Stewart H. The North American survey of placement and adjustment strategies for deep brain stimulation.Stereotact Funct Neurosurg. 2005; 83: 142-147Crossref PubMed Scopus (59) Google Scholar Postoperative imaging is also used to assess for signs of immediate complications such as intracranial haemorrhage. The final stage of surgery is implantation of the IPG under general anaesthesia, which can be done on the same day or at a later stage. The most common location for IPG placement is in the infraclavicular region. The IPG is connected to the extension wire tunnelled from the parietal region to the subcutaneous infraclavicular pocket. Device programming is usually deferred for several weeks after surgical implantation to ensure the ‘microlesion’ effect (transient improvement in symptoms as a result of lead insertion) has subsided. The initial programming session establishes which contacts or pattern of contacts on the DBS lead have the best therapeutic window. This is the difference between the clinical improvement threshold and adverse effect threshold. Once the electrode(s) for chronic stimulation is selected, the amplitude, pulse width, and rate of stimulation are adjusted to achieve optimal therapeutic benefit. Typically, the patient is followed up monthly for the first few months until they are stable clinically. After that, a follow-up at 6- to 12-monthly intervals should be sufficient to assess the battery status, function of device, and to check if further adjustments are needed. These include intracranial haemorrhage, and complications related to both the hardware and stimulation itself. Intracranial haemorrhage is a well-recognised complication of DBS surgery with an incidence of 0.2–12.5%.19Rezai A.R. Machado A.G. Deogaonkar M. et al.Surgery for movement disorders.Neurosurg. 2008; 62: 809-838Crossref PubMed Scopus (2) Google Scholar Intraparenchymal haemorrhage is more common, although epidural and subdural haemorrhage have also been reported. Risk factors associated with an increased risk of haemorrhage include: age, history of hypertension, and use of MER. Careful trajectory planning using neuroimaging to identify small blood vessels can reduce the risks. Hardware-related complications are common and include infection, lead migration, lead fracture, lead and skin erosion, and hardware malfunction. Reported infection rates range from <1% to 15%, typically presenting within 3 months of surgery.19Rezai A.R. Machado A.G. Deogaonkar M. et al.Surgery for movement disorders.Neurosurg. 2008; 62: 809-838Crossref PubMed Scopus (2) Google Scholar Common sites of infection include the IPG pocket, the burr hole site, and the retroauricular connector site. Lead fracture usually occurs at the burr hole site and can result from trauma or if the lead was fixed too tightly around against the skull. However, a too loosely fixed lead can result in lead migration. Stimulation-related complications are generally reversible. Stimulation-related dyskinesia can occur after STN DBS. This is usually managed by adjusting the stimulation parameters or medication. Other complications include worsening of axial symptoms such as balance and gait disturbance, and ocular symptoms. Cognitive and neuropsychiatric complications such as depression, mania, apathy, and hallucinations have been reported. These could be related to stimulation, changes in medication, or the effects of natural disease progression.21Voon V. Kubu C. Krack P. et al.Deep brain stimulation: neuropsychological and neuropsychiatric issues.Mov Disord. 2006; 21: S305-S327Crossref PubMed Scopus (312) Google Scholar STN DBS is superior to GPi DBS in the treatment of PD symptoms and the incidence of drug-induced adverse effects.22Krause M. Fogel W. Heck A. et al.Deep brain stimulation for the treatment of Parkinson’s disease: subthalamic nucleus versus globus pallidus internus.J Neurol Neurosurg Psychiatry. 2001; 70: 464-470Crossref PubMed Scopus (180) Google Scholar Assessment of outcome in DBS for PD is expressed in terms of the reduction of the Unified Parkinson's Disease Rating Scale Part III (UPDRS III) score. The long-term benefit of STN DBS treatment for PD is well-established at 5 yrs after implantation.23Krack P. Batir A. Van Blercom N. et al.Five year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease.N Engl J Med. 2003; 349: 1925-1934Crossref PubMed Scopus (1707) Google Scholar VIM DBS stimulation is a highly effective treatment for ET of the upper limb with demonstrable long-term efficacy. In a small number of patients, efficacy reduces over time, which has been attributed to tolerance of stimulation and disease progression.24Favilla C.G. Ullman D. Shukla A. et al.Worsening essential tremor following deep brain stimulation: disease progression versus tolerance.Brain. 2012; 135: 1455-1462Crossref PubMed Scopus (92) Google Scholar The incidence of dysarthria has been reported to be increased after bilateral compared with unilateral stimulation.23Krack P. Batir A. Van Blercom N. et al.Five year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease.N Engl J Med. 2003; 349: 1925-1934Crossref PubMed Scopus (1707) Google Scholar The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is used to assess treatment outcomes after GPi DBS for dystonia. Bilateral GPi DBS has been demonstrated to be effective with a mean improvement of 50% and 65% in the BFMDRS at 3 months and 2 yrs, respectively. Patients with DYT-1 gene mutation were also shown to have greater benefit from GPi DBS.25Coubes P. Cif L. El Fertit H. et al.Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results.J Neurosurg. 2004; 101: 189-194Crossref PubMed Scopus (316) Google Scholar There has been significant progress in surgery for refractory movement disorders with advances in neuroimaging, device development, and understanding of neurobiology. A multidisciplinary team approach is essential for successful outcome. Recent developments such as gene therapy, fetal and stem-cell transplantation hold promise but much more work is needed.