Parkinson’s disease (PD) is a progressive multi-system, neurodegenerative disease that leads to both motor and non-motor symptoms (1, 2). The most common motor symptoms include tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms include pain, orthostatic hypotension, urinary disturbances, sleep disorders, and various neuropsychiatric symptoms. Both sets of symptoms have significant impact on PD patients’ quality of life and mortality (1, 3, 4). The wide array of PD symptoms has been shown to alter family relationships, lead to a loss of self-identity, and contribute toward a sense of being deprived of one’s self-worth (5). Therapeutic options aimed at alleviating PD symptoms are thus vital for disease management.
Though the exact cause of PD continues to be studied today, there exist two governing markers underlying the pathophysiology of the disease process. These include the degeneration of dopaminergic neurons in the nigrostriatal pathway, and the presence of intracytoplasmic proteinaceous inclusion bodies in surviving neurons, referred to as Lewy bodies. The degeneration of dopaminergic neurons in the nigrostriatal pathway is thought to reduce inhibition of the thalamus and decrease excitatory input to the motor cortex, ultimately leading to bradykinesia and other PD symptoms (6, 7). The decrease in dopaminergic neural firing in the nigrostriatal pathway may disrupt the neural oscillations in the basal ganglia. Specifically, it may lead to increased firing of striatal neurons in the indirect pathway, with the recruited neurons firing with an excess of beta (13–30 Hz) oscillations in the motor system (8). The two mainstay therapies of PD, dopamine and deep brain stimulation (DBS), have both been shown to alter the pathological changes in electrical oscillations (9, 10).
Though dopamine and DBS are the gold standard treatment for PD, they both continue to have severe limitations and side effects to consider. For dopamine treatment, side effects include dyskinesias, GI disturbances, orthostatic hypotension, and neuropsychiatric features including anxiety and hallucinations (11). While it is possible to adjust dosing parameters to ameliorate some of the side effects above, one of the more prominent issues is that dopamine agonists are associated with loss of efficacy over time (12). DBS has been shown to have excellent outcomes in alleviating some of the motor and non-motor symptoms of PD (13–15). However, there are several associated risks with DBS, including intracranial bleeding (up to 5.0%), hardware issues, infection, incorrect placement, mal-positioning, and seizures (up to 2.4%) (13, 16). The risk of infection has been reported to range from 1.2 to 15.2% (13). Similar to dopamine treatment, the use of DBS may have decreased efficacy over time as well (17). DBS has also been shown to lead to neurologic side effects such as memory deficits, speech disturbances, dysphagia, and motor & sensory issues. There are also a wide array of psychological side effects, such as mania, depression and suicidal ideation (13, 18).
An alternate therapy that can be used to alleviate both motor and non-motor symptoms of PD is spinal cord stimulation (SCS) technology. Spinal cord stimulation of the dorsal columns within the epidural space has already been shown to be beneficial in a multitude of pain conditions (19, 20). SCS has been shown to stimulate large non-nociceptive myelinated fibers of the peripheral nerves (A-β fibers), leads to inhibition of the small nociceptive projections (A-δ and C) in the dorsal horn. Additionally, SCS may lead to the release of GABA, substance-P and serotonin, neurotransmitters involved in pain modulation (19). The new therapy has also been shown to improve the motor symptoms of PD (21, 22). Thus, SCS may be an excellent therapeutic option to alleviate both motor symptoms and non-motor symptoms such as pain in PD patients. Whether to use SCS as a singular bioelectric therapy option or as a salvage therapy after dopamine and DBS treatments have begun to lose efficacy, continues to be a question of interest. There have been studies that have shown SCS to be a reasonable salvage option after dopamine and DBS (23). The data thus far point to SCS as being a viable alternative, conjunctive and or potential salvage therapy for those with PD. This paper aims to analyze clinical translational data for SCS in PD as both singular bioelectric therapy and salvage therapy after loss of efficacy of DBS for both motor and non-motor symptoms such as pain.