Deep brain stimulation for Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe neurosurgical symptomatic therapy for eligible patients with advanced disease in whom medical treatment fails to provide adequate symptom control and good quality of life, or in whom dopaminergic medications induce severe side effects such as dyskinesias. DBS can be tailored to the patient's symptoms and targeted to various nodes along the basal ganglia-thalamus circuitry, which mediates the various symptoms of the illness; DBS in the thalamus is most efficient for tremors, and DBS in the pallidum most efficient for rigidity and dyskinesias, whereas DBS in the subthalamic nucleus (STN) can treat both tremors, akinesia, rigidity and dyskinesias, and allows for decrease in doses of medications even in patients with advanced stages of the disease, which makes it the preferred target for DBS. However, DBS in the STN assumes that the patient is not too old, with no cognitive decline or relevant depression, and does not exhibit severe and medically resistant axial symptoms such as balance and gait disturbances, and falls. Dysarthria is the most common side effect of DBS, regardless of the brain target. DBS has a long-lasting effect on appendicular symptoms, but with progression of disease, nondopaminergic axial features become less responsive to DBS. DBS for PD is highly specialised; to enable adequate selection and follow-up of patients, DBS requires dedicated multidisciplinary teams of movement disorder neurologists, functional neurosurgeons, specialised DBS nurses and neuropsychologists.

Keywords: Parkinson's disease; deep brain stimulation; globus pallidus; pallidotomy; subthalamic nucleus; thalamotomy.

Fig. 1

Appearance of substantia nigra compacta (SNc) in a person without and a person with Parkinson's disease (PD). (a) Macroscopic view of healthy pigmented SNc (arrows). (b) Loss of neurons leads to loss of pigmentation of the SNc (arrows). (c) Histology of SNc in a person without PD shows a dense network of melanin‐pigmented dopaminergic neurons. (d) Loss of dopaminergic neurons in a person with PD; the cell in the black square shows a cytoplasmic protein aggregate called Lewy body (figure adapted from the dissertation ‘Genetic analysis of dopaminergic neuron survival’ by Liviu Aron, PhD, with kind permission from the author).

Fig. 2

Simplified basal ganglia‐thalamo‐cortical circuitry in Parkinson's disease (PD) and rationale for deep brain stimulation (DBS) in various targets: in PD there is an imbalance between gabaergic inhibitory pathways and glutamatergic excitatory pathways. Death of dopaminergic cells in the substantia nigra compacta (SNc) leads to depletion of dopamine in the corpus striatum (caudate and putamen). This leads to changes in the output of the striatum towards the globus pallidus along two pathways; in the indirect pathways, the striatum increases its gabaergic inhibition of the globus pallidus externus (GPe), which leads to a decreased inhibition of the GPe on the subthalamic nucleus (STN). The STN then becomes overactive and exerts an increased glutamatergic excitation on the globus pallidus internus (GPi) and on the substantia nigra reticulata (SNr), both of which become overactive. At the same time, there is a decrease in the striatum's inhibitory activity on the GPi through the direct pathway, leading to further increase of the inhibitory activity of the GPi. The highly overactive GPi then exerts an increased inhibition on the motor thalamus, the activity of which is decreased on the cortex. There is also increased inhibition on brain stem nuclei including the locomotor centre in the pedunculopontine nucleus (PPN). The net effect is the akinesia, rigidity and tremors of PD. Hence, the rationale for targeting the GPi or the STN by high‐frequency DBS is to decrease their pathological overactivity, which would thus contribute to restoring normal movement patterns in patients with PD.

Fig. 3

Anatomical template of basal ganglia and thalamus with three quadripolar leads in situ, one in the VIM, one in the STN and one in the GPi. Abbreviations: DBS, deep brain stimulation; GPi, globus pallidus internus; SNr, substantia nigra reticulata; STN, subthalamic nucleus; VIM, ventral intermediate nucleus of the thalamus.