Chapter 16 - Deep brain stimulation: state of the art and novel stimulation targets
Introduction
Surgery for Parkinson’s disease (PD) initially focused on treating tremor. Early treatments were ablative, producing lesions in the brain using open or stereotactic techniques in the subcortical structures, the basal ganglia, and the thalamus. Since the 1950s, neurosurgeons have performed temporary and reversible focal inactivations or modulations of the intrinsic neural elements prior to making lesions. These tests used a variety of strategies, including injections of local anesthetics, cooling, or electrical stimulation, to both predict efficacy and warn of potential adverse effects with permanent lesions. It is in the course of these tests that the therapeutic effects of electrical stimulation were characterized. Benabid expanded and pursued the observation that tremor was reliably arrested during high-frequency stimulation in the thalamus (Benabid et al., 1987, Benabid et al., 1989). He applied the same principle to another structure, the subthalamic nucleus (STN), and showed improvement of tremor, rigidity, and bradykinesia, as well as a reduction in the required levadopa dose (Benabid et al., 1994). Others targeted additional structures, including sites in the basal ganglia, thalamus, and cortex, and their input and output pathways.
The use of deep brain stimulation (DBS) became widespread in the late 1990s, and several large studies have subsequently confirmed the efficacy and safety profile of the procedure (Burchiel et al., 1999, Deuschl et al., 2006, Hariz et al., 2008, Krack et al., 2003, Rodriguez-Oroz et al., 2005). Recently, a multicenter randomized controlled trial of DBS versus medical therapy concluded that, at 6 months, the surgery was more effective in improving motor function, quality of life, and reducing dyskinesias (Weaver et al., 2009).
DBS has become an established tool in the management of patients with advanced PD. This review highlights the benefits and limitations of DBS in various brain targets and discusses some of the understanding of the mechanism of action.
Section snippets
Benefits
Unlike ablative procedures, adjustable settings for DBS allow for maximization of benefits and minimization of side effects. This, combined with the low morbidity of the procedure, has contributed to the appeal of DBS. For such reasons, ablative procedures have now largely been replaced by DBS. The DBS targets most often used to treat PD are the STN and the globus pallidus internus (GPi). The choice between GPi and STN continues to be evaluated, and the best target still needs to be defined
Contraindications
Contraindications to functional neurosurgical intervention include serious systemic medical co-morbitidies such as unstable heart disease, active infection, disabling cerebrovascular disease, or malignancy associated with markedly reduced life expectancy (Lang et al., 2006a). Candidates for surgery should have symptoms consistent with idiopathic PD without evidence of extensive multiple system involvement, since DBS is generally not effective in patients with non-levodopa responsive features.
Limitations of therapy
The recent pathological characterization of α-synuclein-positive inclusions has provided a neuroanatomical basis for the symptoms of PD that predate the motor phase of the illness, as well as the symptoms that appear later in the disease course. The availability of antibodies to α-synuclein has allowed the mapping out of inclusion pathology throughout the neuraxis in patients with PD. There is a good correlation between the presence and distribution of such inclusions and the symptomatology in
Novel stimulation targets
Dopaminergic motor symptoms represent only one facet of the disease, and as the chronological sequence of pathological events is becoming better characterized, there is an increasing appreciation of both the so-called non-motor components of the illness as well as the non-dopaminergic components. These include disorders of sleep and cognition, depression, olfactory disturbances, autonomic disturbances, gait and postural disturbances. It has been challenging to delineate the neuroanatomical
Mechanism of action
Despite two decades having passed since the introduction of DBS, the precise mechanism of action remains unclear (Gradinaru et al., 2009). The effects of stimulation of the STN and GPi are similar to the effects of ablative procedures, though the reversibility of stimulation indicates that the effect is not due to a permanent lesion. This has been supported by primate studies, showing only 5% decrease in cell count after 7 months of high-frequency stimulation (Wallace et al., 2007), as well as
Conclusions
DBS offers relief of the cardinal symptoms similar to the best response to levodopa, without the adverse side effects. Good candidate patients for DBS surgery continue to respond to levodopa but are disabled by the motor complications of medication therapy. The clinical benefits of DBS are likely due to disruption of the pathological activity in the cortical-thalamic-basal ganglia-cortical motor loop, and symptoms unrelated to this circuit, such as mood, cognition, gait, and posture, are
Acknowledgments
AML is a Canada Research Chair (tier 1) in Neuroscience.
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2020, World NeurosurgeryCitation Excerpt :Deep brain stimulation (DBS) is an accepted standard of care for treating medically refractory movement disorders such as Parkinson disease (PD).1,2
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2018, Parkinsonism and Related DisordersA brain network model explaining tremor in Parkinson's disease
2016, Neurobiology of DiseaseCitation Excerpt :In PD patients, the precentral and postcentral gyri contralateral to movement, the SMA, the ipsilateral cerebellar cortex, and the cerebellar vermis are shown to be activated during movement (Duffau et al., 1996). These are the same regions involved in the execution of voluntary repetitive movements of the hand in the normal subjects mentioned above (Colebatch et al., 1991; Deiber et al., 1991; Friston et al., 1992). In addition to cortical involvement, movement related potentials associated with hand movements were recorded in the thalamus of PD patients (Paradiso et al., 2004; Rektor et al., 2001a).
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2015, Brain StimulationCitation Excerpt :It is estimated that over 100,000 patients worldwide have been implanted with DBS systems, with the rate of annual accrual increasing [1]. DBS has proven to be remarkably effective in treating a range of neurological disorders including Parkinson's disease (PD), essential tremor, dystonia and is currently being evaluated in pain and psychiatric illness [2–6]. Recently, the potential beneficial effects of DBS have been reported for memory enhancement in rodents [7–10] and humans [11–14] and thus has implications for therapeutic applications.