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StimRouter: Expanding the Neuromodulation Frontier

Although PNS is used for all kinds of medical conditions, ranging from chronic neuropathic pain and headache to epilepsy, depression, hypertension and heart failure, its importance is frequently overshadowed by spinal cord stimulation and deep brain stimulation. While the earlier version of this book dealt exclusively with various pain syndromes, this new volume covers the entire spectrum of PNS applications. Written by recognized authorities in their respective fields, the chapters of this title describe the use of PNS in the management of neurological, psychiatric, otorhinolaryngological, cardiovascular, pulmonary, colorectal and genitourinary disorders.

To reflect the complexity of the regulatory process, the book ends with a special chapter dedicated to the current state of approval of different PNS devices.

Stimulation of the Peripheral Nervous System

This book will be of great value to all those who deal with neuromodulation, including clinicians who select PNS candidates, surgeons and other specialists who implant PNS devices, and researchers and engineers who work on making the stimulators safer and more effective. Dr Athmaja R. Like this: Like Loading Neuromodulation is "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body".

It is carried out to normalize — or modulate — nervous tissue function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli such as a magnetic field rTMS , an electric current , or a drug instilled directly in the subdural space intrathecal drug delivery.

Emerging applications involve targeted introduction of genes or gene regulators and light optogenetics , and by , these had been at minimum demonstrated in mammalian models, or first-in-human data had been acquired. Neuromodulation, whether electrical or magnetic, employs the body's natural biological response by stimulating nerve cell activity that can influence populations of nerves by releasing transmitters, such as dopamine , or other chemical messengers such as the peptide Substance P , that can modulate the excitability and firing patterns of neural circuits.

There may also be more direct electrophysiological effects on neural membranes as the mechanism of action of electrical interaction with neural elements. The end effect is a "normalization" of a neural network function from its perturbed state. Presumed mechanisms of action for neurostimulation include depolarizing blockade, stochastic normalization of neural firing , axonal blockade , reduction of neural firing keratosis, and suppression of neural network oscillations. Existing and emerging neuromodulation treatments also include application in medication-resistant epilepsy , [3] chronic head pain conditions, and functional therapy ranging from bladder and bowel or respiratory control to improvement of sensory deficits, such as hearing cochlear implants and auditory brainstem implants and vision retinal implants.

Stimulation of the Peripheral Nervous System - Table of Contents - Karger Publishers

Neuromodulation therapy has been investigated for other chronic conditions, such as Alzheimer's disease , [8] [9] depression , chronic pain, [10] [11] and as an adjunctive treatment in recovery from stroke. Electrical stimulation using implantable devices came into modern usage in the s and its techniques and applications have continued to develop and expand. The stimulator, with the battery, similar to a pacemaker, may also be implanted, or may remain outside the body.

In general, neuromodulation systems deliver electrical currents and typically consist of the following components: An epidural, subdural or parenchymal electrode placed via minimally invasive needle techniques so-called percutaneous leads or an open surgical exposure to the target surgical "paddle" or "grid" electrodes , or stereotactic implants for the central nervous system, and an implanted pulse generator IPG.

Depending on the distance from the electrode access point an extension cable may also be added into the system. The IPG can have either a non-rechargeable battery needing replacement every 2—5 years depending on stimulation parameters or a rechargeable battery that is replenished via an external inductive charging system.

Although most systems operate via delivery of a constant train of stimulation, there is now the advent of so-called "feed-forward" stimulation where the device's activation is contingent on a physiological event, such as an epileptic seizure. In this circumstance, the device is activated and delivers a desynchronizing pulse to the cortical area that is undergoing an epileptic seizure. This concept of feed-forward stimulation will likely become more prevalent as physiological markers of targeted diseases and neural disorders are discovered and verified.

New electrode designs could yield more efficient and precise stimulation, requiring less current and minimizing unwanted side-stimulation. In addition, to overcome the challenge of preventing lead migration in areas of the body that are subject to motion such as turning and bending, researchers are exploring developing small stimulation systems that are recharged wirelessly rather than through an electrical lead. Spinal cord stimulation is a form of invasive neuromodulation therapy in common use since the s. Its principal use is as a reversible, non-pharmacological therapy for chronic pain management that delivers mild electrical pulses to the spinal cord.

It delivers mild impulses along slender electrical leads leading to small electrical contacts, about the size of a grain of rice, at the area of the spine to be stimulated. Kilohertz stimulation trains have been applied to both the spinal cord proper as well as the dorsal root ganglion in humans. All forms of spinal cord stimulation have been shown to have varying degrees of efficacy to address a variety of pharmacoresistant neuropathic or mixed neuropathic and noiciceptive pain syndromes such as post-laminectomy syndrome, low back pain, complex regional pain syndrome, peripheral neuropathy, peripheral vascular disease and angina.

The general process for spinal cord stimulation involves a temporary trailing of appropriate patients with an external pulse generator attached to epidural electrodes located in the lower thoracic spinal cord. The electrodes are placed either via a minimally invasive needle technique so-called percutaneous leads or an open surgical exposure surgical "paddle" electrodes. Patient selection is key, and candidates should pass rigorous psychological screening as well as a medical workup to assure that their pain syndrome is truly medication-resistant. Depending on the system, the program may elicit a tingling sensation that covers most of the painful area, replacing some of the painful sensations with more of a gentle massaging sensation, although other more recent systems do not create a tingling sensation.

The patient is sent home with a handheld remote controller to turn the system off or on or switch between pre-set stimulation parameters, and can follow up to adjust the parameters. Another invasive neuromodulation treatment developed in the s is deep brain stimulation , which may be used to help limit symptoms of movement disorder in Parkinson's disease , dystonia , or essential tremor.

Food and Drug Administration in for essential tremor, in for Parkinson's disease, and received a humanitarian device exemption from the FDA in for motor symptoms of dystonia. It has also shown promise for Tourette syndrome, torticollis, and tardive dyskinesia. DBS therapy, unlike spinal cord stimulation, has a variety of central nervous system targets, depending on the target pathology. For Parkinson's disease central nervous system targets include the subthalamic nucleus, globus pallidus interna, and the ventral intermidus nucleus of the thalamus.

Dystonias are often treated by implants targeting globus pallidus interna, or less often, parts of the ventral thalamic group. The anterior thalamus is the target for epilepsy. These methods use external electrodes to apply a current to the body in order to change the functioning of the nervous system.

The Central Nervous System: The Brain and Spinal Cord

Magnetic methods of neuromodulation are normally non-invasive: no surgery is required to allow a magnetic field to enter the body because the magnetic permeability of tissue is similar to that of air. In other words: magnetic field penetrate the body very easily. The two main techniques are highly related in that both use changes in magnetic field strength to induce electric fields and ionic currents in the body. There are however differences in approach and hardware.

In rTMS the stimulation has a high amplitude 0. In tPEMF the stimulation has a low amplitude 0. Chemical neuromodulation is always invasive, because a drug is delivered in a highly specific location of the body. The non-invasive variant is traditional pharmacotherapy , e. Electrical stimulation of the nervous system has a long and complex history. Earlier practitioners of deep brain stimulation in the latter half of the 20th century Delgado, Heath, Hosbuchi. See Hariz et al. Heath, in the s, stimulated subcortical areas and made detailed observations of behavioral changes.

A new understanding of pain perception was ushered in in , with the Gate Theory of Wall and Melzack.

References

Building on that concept, in , the first dorsal column stimulator for pain control was demonstrated by Dr. In , Hosbuchi reported alleviating the denervation facial pain of anesthesia dolorosa through ongoing electrical stimulation of the somatosensory thalamus, marking the start of the age of deep brain stimulation. Despite the limited clinical experience in these decades, that era is remarkable for the demonstration of the role technology has in neuromodulation, and there are some case reports of deep brain stimulation for a variety of problems; real or perceived.

Delgado hinted at the power of neuromodulation with his implants in the bovine septal region and the ability of electrical stimulation to blunt or alter behavior. Further attempts at this "behavioral modification" in humans were difficult and seldom reliable, and contributed to the overall lack progress in central nervous system neuromodulation from that era. Attempts at intractable pain syndromes were met with more success, but again hampered by the quality of technology.

In particular, the so-called DBS "zero" electrode, consisting of a contact loop on its end had an unacceptable failure rate and revisions were fraught with more risk than benefit. Overall, attempts at using electrical stimulation for "behavioral modification" were difficult and seldom reliable, slowing development of DBS.

Attempts at addressing intractable pain syndromes with DBS were met with more success, but again hampered by the quality of technology. A number of physicians who hoped to address hitherto intractable problems sought development of more specialized equipment; for instance, in the s, Wall's colleague Bill Sweet recruited engineer Roger Avery to make an implantable peripheral nerve stimulator. Avery started the Avery Company, which made a number of implantable stimulators. Shortly before his retirement in , he submitted data requested by the FDA, which had begun to regulate medical devices following a meeting on the topic, regarding DBS for chronic pain.

Medtronic and Neuromed also made deep brain stimulators at the time, but reportedly felt a complex safety and efficacy clinical trial in patients who were difficult to evaluate would be too costly for the size of the potential patient base, so did not submit clinical data on DBS for chronic pain to the FDA, and that indication was de-approved.

However, near this time in France and elsewhere, DBS was investigated as a substitute for lesioning of brain nuclei to control motor symptoms of movement disorders such as Parkinson's disease, and by the mids, this reversible, non-destructive stimulation therapy had become the primary application of DBS in appropriate patients, to slow progression of movement impairment from the disease and reduce side effects from long-term, escalating medication use.

In parallel to the development of neuromodulation systems to address motor impairment, cochlear implants were the first neuromodulation system to reach a broad commercial stage to address a functional deficit; they provide sound perception in users who are hearing-impaired due to missing or damaged sensory cells cilia in the inner ear. The approach to electrical stimulation used in cochlear implants was soon modified by one manufacturer, Boston Scientific Corporation, for design of electrical leads to be used in spinal cord stimulation treatment of chronic pain conditions.

In , the global pharmaceutical company GlaxoSmithKline announced an initiative in bioelectric medicine in which the autonomic nervous system's impact on the immune system and inflammatory disease might be treated through electrical stimulation rather than pharmaceutical agents. The company's first investment in involved a small startup company, SetPoint Medical, which was developing neurostimulators to address inflammatory autoimmune disorders such as rheumatoid arthritis.

Ultimately, the electroceuticals quest aims to find the electro-neural signature of disease and at a cellular level, in real time, play back the more normal electro-signature to help maintain the neural signature in the normal state. Unlike preceding neuromodulation therapy methods, the approach would not involve electrical leads stimulating large nerves or spinal cords or brain centers. It might involve methods that are emerging within the neuromodulation family of therapies, such as optogenetics or some new nanotechnology. Disease states and conditions that have been discussed as targets for future electroceutical therapy include diabetes, infertility, obesity, rheumatoid arthritis, and autoimmune disorders.

Neuromodulation (medicine)

From Wikipedia, the free encyclopedia. Neuromodulation [ edit on Wikidata ].


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Main article: Spinal cord stimulation. Main article: Deep brain stimulation.

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