Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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With continuous progress and rapid technological advancement of neuromodulation it is conceivable that within next decade or so, our approach to the electrical stimulation of the spinal cord used in treatment of chronic pain will change radically. The currently used spinal cord stimulation (SCS), with its procedural invasiveness, bulky devices, simplistic stimulation paradigms, and frustrating decline in effectiveness over time will be replaced by much more refined and individually tailored modality. ⋯ Based on the information available today, this article will summarize emerging applications of SCS in the treatment of pain and theorize on further developments that may be introduced in the foreseeable future. An overview of clinical and technological innovations will serve as a basis for better understanding of SCS landscape for the next several years.
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Deep brain stimulation (DBS) is an implanted electrical device that modulates specific targets in the brain resulting in symptomatic improvement in a particular neurologic disease, most commonly a movement disorder. It is preferred over previously used lesioning procedures due to its reversibility, adjustability, and ability to be used bilaterally with a good safety profile. Risks of DBS include intracranial bleeding, infection, malposition, and hardware issues, such migration, disconnection, or malfunction, but the risk of each of these complications is low--generally ≤ 5% at experienced, large-volume centers. ⋯ Brain targets implanted include the thalamus (most commonly for essential tremor), subthalamic nucleus (most commonly for Parkinson's disease), and globus pallidus (Parkinson's disease and dystonia), although new targets are currently being explored. Future developments include brain electrodes that can steer current directionally and systems capable of "closed loop" stimulation, with systems that can record and interpret regional brain activity and modify stimulation parameters in a clinically meaningful way. New, image-guided implantation techniques may have advantages over traditional DBS surgery.
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The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Macrophages and microglia can be polarized into the classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype. Programmed cell death 1 (PD-1) is a critical immune inhibitory receptor involved in innate and adaptive immune responses. ⋯ Therefore, our results suggest that PD-1 signaling plays an important role in the regulation of macrophage/microglial polarization. Thus, deregulated PD-1 signaling may induce the polarization of macrophages/microglia toward the M1 phenotype. Overall, our results provide new insights into the modulatory mechanisms of macrophage/microglial polarization, thereby possibly facilitating the development of new therapies for SCI via the regulation of macrophage/microglial polarization through PD-1 signaling.
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Epidural spinal cord stimulation (SCS) is currently proposed to treat intractable neuropathic pain. Since the 1970s, isolated cases and small cohorts of patients suffering from dystonia, tremor, painful leg and moving toes (PLMT), or Parkinson’s disease were also treated with SCS in the context of exploratory clinical studies. Despite the safety profile of SCS observed in these various types of movement disorders, the degree of improvement of abnormal movements following SCS has been heterogeneous among patients and across centers in open-label trials, stressing the need for larger, randomized, double-blind studies. This article provides a comprehensive review of both experimental and clinical studies of SCS application in movement disorders.
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Historical Article
Use of cortical stimulation in neuropathic pain, tinnitus, depression, and movement disorders.
Medical treatment must strike a balance between benefit and risk. As the field of neuromodulation develops, decreased invasiveness, in combination with maintenance of efficacy, has become a goal. We provide a review of the history of cortical stimulation from its origins to the current state. ⋯ The third part focuses on major depression. The fourth section concludes with the discussion of the use of cortical stimulation in movement disorders. Each part discusses the development of the field, describes the current care protocols, and suggests future avenues for research needed to advance neuromodulation.