Elsevier

The Lancet Neurology

Volume 8, Issue 1, January 2009, Pages 67-81
The Lancet Neurology

Review
Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease

https://doi.org/10.1016/S1474-4422(08)70291-6Get rights and content

Summary

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN-HFS) is the preferred surgical treatment for advanced Parkinson's disease. In the 15 years since its introduction into clinical practice, many studies have reported on its benefits, drawbacks, and insufficiencies. Despite limited evidence-based data, STN-HFS has been shown to be surgically safe, and improvements in dopaminergic drug-sensitive symptoms and reductions in subsequent drug dose and dyskinesias are well documented. However, the procedure is associated with adverse effects, mainly neurocognitive, and with side-effects created by spread of stimulation to surrounding structures, depending on the precise location of electrodes. Quality of life improves substantially, inducing sudden global changes in patients' lives, often requiring societal readaptation. STN-HFS is a powerful method that is currently unchallenged in the management of Parkinson's disease, but its long-term effects must be thoroughly assessed. Further improvements, through basic research and methodological innovations, should make it applicable to earlier stages of the disease and increase its availability to patients in developing countries.

Introduction

In 1987, the discovery that high-frequency deep brain stimulation (DBS) was able to mimic, in a reversible and adjustable manner, the effects of ablation of functional targets has revived functional neurosurgery of movement disorders, thus allowing clinicians to target areas suggested by basic neuroscience, such as the subthalamic nucleus (STN; figure 1).1, 2, 3 In the first patients with advanced Parkinson's disease (PD) to receive high-frequency stimulation of the STN (STN-HFS) in 1993,4, 5 tremor, rigidity, and bradykinesia improved significantly, thus allowing levodopa doses to be decreased by an average of 60%.6 This reduction in turn alleviated levodopa-induced motor fluctuations and dyskinesias.7 Since then, several thousands of patients all over the world have received STN-HFS implants and shown marked improvements, making this method the reference surgical procedure for advanced PD. Many reports of clinical experience with this procedure have been published, and have documented how the method has rapidly become an established therapy.

In this Review, we briefly describe the surgical techniques used and provide an overview of the prognostic factors and clinical improvements of patients with PD. We also discuss the limitations and morbidity associated with STN-HFS, and explore its clinical efficiency and areas that need to be improved, in addition to future progress and potential successors.

Section snippets

Surgical procedure

The surgical procedure itself varies between neurosurgery teams, depending on their equipment and usual practices. The aim of pre-operative imaging is to determine the best location for target stimulation (figure 2). Stereotactic ventriculography is still used by some teams, although many do not use it because of concern over complications or because they consider MRI localisation to be satisfactory. The problem of MRI distortion, which is the main reason why ventriculography is still used, has

Mechanism of action

The mechanism of action of high-frequency DBS is still not clear, even 21 years after its introduction. The mechanism is believed to be independent of the target, because DBS mimics the effects of ablation in all targets used to date, but its effects depend on stimulation rather than on the creation of a lesion. Several submechanisms are probably involved in producing functional inhibition: (1) a jamming of the neuronal message transmitted through the stimulated structure9 and desynchronisation

Indications

Patients who are thought to benefit from STN-HFS are those affected by clinically diagnosed idiopathic PD, in whom the cardinal symptoms of the disease—bradykinesia, rigidity, and tremor—are likely to be significantly improved.5, 6, 21, 22 Those who show improvement with the optimum adjustment of anti-PD drugs or suprathreshold levodopa dose (300 mg per dose) are highly likely to show a similar improvement after optimum placement of the electrodes into the STN.23 Higher baseline scores on

Clinical outcome

Since the first application of STN-HFS in 1993, several thousand patients worldwide have received implants. Many papers have reported clinical results and provided accumulated evidence on the clinical outcome of STN-HFS, although large series and prospective multicentre clinical trials are rare.

Surgical complications and side-effects

Table 2 summarises the complications that have been related to the surgical procedure. Reviews have produced rather too general a summary,32, 40 and, contrary to data on improvements, outcomes varied widely between centres (table 2),72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92 which might be due to differences in expertise or methods. However, definitions of complications were not the same between reports and were not exclusive (a patient might have several

Other targets

STN-HFS mainly improves levodopa-sensitive symptoms. Midline symptoms, dysautonomic symptoms, and gait disturbance unresponsive to levodopa (ie, freezing)25 are only slightly improved, if at all. Thus, randomised controlled trials are currently underway to compare the outcome of surgery involving the GPi versus the STN, to reassess old targets (ie, centre median–parafascicular complex of the thalamus), and to assess new targets (ie, radiation prelemniscalis, caudal zona incerta, and

Unanswered questions and future research

STN-HFS is currently widely thought of as the surgical method of choice for patients with advanced PD. The benefits of STN-HFS are due to combined mechanisms and probably involve several adjacent structures, including the STN itself. To improve the success of the procedure, more selectivity is needed, both at the topographical level with newly designed electrodes and rechargeable batteries, and at the level of stimulation from the pulse sequence to the pulse waveform.172 All hardware components

Search strategy and selection criteria

PubMed was searched from January, 1993, to October, 2008. Only original articles in English were considered for inclusion. Combinations of the following search terms were used: “STN”, “DBS”, “complications”, and “PD”. Data were also recovered from other sources, such as recent reviews or meta-analyses. As the purpose of the Review was not a meta-analysis, but a general overview of STN DBS, we have taken all information available in the reviewed papers, if needed, even if they were devoted

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