Spinal cord stimulation: therapeutic benefits and movement generation after spinal cord injury.

Spinal cord injury (SCI) is a devastating neurological condition that leads to loss of motor and sensory function. It commonly causes impairments in limb movements, respiration, bowel and bladder function, as well as secondary complications including pain, spasticity, and pressure ulcers. Numerous interventions such as neuroprotection, regeneration, pharmacology, rehabilitation training, and functional electrical stimulation are under investigation for improving function after SCI. This chapter discusses the use of spinal cord stimulation (epidural and intraspinal electrical stimulation) for alleviating pain and spasticity, and restoring standing and walking. Epidural stimulation is effective in reducing the intensity of intractable pain, but its effectiveness in the treatment of spasticity remains unclear. It can induce rhythmic, locomotor-like movements in the legs, presumably due to the activation of afferent pathways. Intraspinal microstimulation is a new electrical stimulation approach that activates locomotor-related networks within the ventral regions of the lumbosacral spinal cord. In animals, this approach is capable of producing prolonged, fatigue-resistant standing and stepping of the hindlegs. While the results in animals have been very encouraging, technical advancements are necessary prior to its implementation in humans with SCI. Taken collectively, spinal cord stimulation holds substantial promise in restoring function after neural injury or disease.

[1]  K. R. Robinson,et al.  The distribution of free calcium in transected spinal axons and its modulation by applied electrical fields , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  M. Fehlings,et al.  The effect of direct-current field on recovery from experimental spinal cord injury. , 1988, Journal of neurosurgery.

[3]  Tapping into the Spinal Cord for Restoring Function after Spinal Cord Injury , 2007 .

[4]  Sherif M. Elbasiouny,et al.  Management of Spasticity After Spinal Cord Injury: Current Techniques and Future Directions , 2010, Neurorehabilitation and neural repair.

[5]  H. W. Beams,et al.  In vitro control of growing chick nerve fibers by applied electric currents. , 1946, Journal of cellular and comparative physiology.

[6]  M. Dimitrijevic,et al.  Evidence for a Spinal Central Pattern Generator in Humans a , 1998, Annals of the New York Academy of Sciences.

[7]  V. Mushahwar,et al.  A Physiologically-based Controller for Generating Overground Locomotion using Functional Electrical Stimulation , 2007 .

[8]  D. McCrea,et al.  Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation , 2006, The Journal of physiology.

[9]  Frank Rattay,et al.  Posterior root–muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord , 2007, Muscle & nerve.

[10]  A. Prochazka,et al.  Intraspinal micro stimulation generates locomotor-like and feedback-controlled movements , 2002, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[11]  S. Piantadosi,et al.  Spinal Cord Stimulation versus Repeated Lumbosacral Spine Surgery for Chronic Pain: A Randomized, Controlled Trial , 2005, Neurosurgery.

[12]  Grace C Y Peng,et al.  Toward Neurotechnology Innovation: Report from the 2005 Neural Interfaces Workshop. An NIH‐Sponsored Event , 2006, Neuromodulation : journal of the International Neuromodulation Society.

[13]  A. Duenas,et al.  Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation. , 2009, Health Technology Assessment.

[14]  R. Burke,et al.  The use of state-dependent modulation of spinal reflexes as a tool to investigate the organization of spinal interneurons , 1999, Experimental Brain Research.

[15]  Arthur Prochazka,et al.  Control of urinary bladder function with devices: successes and failures. , 2006, Progress in brain research.

[16]  Charles Tator,et al.  Effect of alternating current stimulation of the spinal cord on recovery from acute spinal cord injury in rats. , 1987, Surgical neurology.

[17]  V. Mushahwar,et al.  Intraspinal microstimulation generates functional movements after spinal-cord injury , 2004, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[18]  Christine Haberler,et al.  No tissue damage by chronic deep brain stimulation in Parkinson's disease , 2000, Annals of neurology.

[19]  Igor A. Lavrov,et al.  Epidural spinal cord stimulation plus quipazine administration enable stepping in complete spinal adult rats. , 2007, Journal of neurophysiology.

[20]  M. Dimitrijevic,et al.  Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials , 2004, Spinal Cord.

[21]  Y. Lazorthes,et al.  Chronic intrathecal baclofen administration for control of severe spasticity. , 1990, Journal of neurosurgery.

[22]  V. Mushahwar,et al.  Selective activation of muscle groups in the feline hindlimb through electrical microstimulation of the ventral lumbo-sacral spinal cord. , 2000, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[23]  S. Garfin,et al.  Organization of intrathecal nerve roots at the level of the conus medullaris. , 1990, The Journal of bone and joint surgery. American volume.

[24]  E Jankowska,et al.  Direct and indirect activation of nerve cells by electrical pulses applied extracellularly. , 1976, The Journal of physiology.

[25]  R. Deyo,et al.  Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications , 2004, Pain.

[26]  E. Henneman.  The size-principle: a deterministic output emerges from a set of probabilistic connections. , 1985, The Journal of experimental biology.

[27]  P. Nelson,et al.  Oscillating field stimulation for complete spinal cord injury in humans: a phase 1 trial. , 2005, Journal of neurosurgery. Spine.

[28]  Changfeng Tai,et al.  Bladder and urethral sphincter responses evoked by microstimulation of S2 sacral spinal cord in spinal cord intact and chronic spinal cord injured cats , 2004, Experimental Neurology.

[29]  Vivian K Mushahwar,et al.  The effects of intraspinal microstimulation on spinal cord tissue in the rat. , 2010, Biomaterials.

[30]  Michael G. Fehlings,et al.  The effect of direct current field polarity on recovery after acute experimental spinal cord injury , 1992, Brain Research.

[31]  T. Nichols,et al.  Distribution of heterogenic reflexes among the quadriceps and triceps surae muscles of the cat hind limb. , 2003, Journal of neurophysiology.

[32]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[33]  L. Jaffe,et al.  Neurites grow faster towards the cathode than the anode in a steady field. , 1979, The Journal of experimental zoology.

[34]  Shealy Cn,et al.  Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. , 1967 .

[35]  Kenneth W. Horch,et al.  Intraspinal microstimulation using cylindrical multielectrodes , 2006, IEEE Transactions on Biomedical Engineering.

[36]  M. Dimitrijevic,et al.  Human lumbar cord circuitries can be activated by extrinsic tonic input to generate locomotor-like activity. , 2007, Human movement science.

[37]  A. Blight,et al.  Functional recovery after spinal cord hemisection in guinea pigs: The effects of applied electric fields , 1990, The Journal of comparative neurology.

[38]  R. Taylor.  Spinal cord stimulation in complex regional pain syndrome and refractory neuropathic back and leg pain/failed back surgery syndrome: results of a systematic review and meta-analysis. , 2006, Journal of pain and symptom management.

[39]  V. Pikov,et al.  Mapping of spinal cord circuits controlling the bladder and external urethral sphincter functions in the rabbit , 2004, Neurourology and urodynamics.

[40]  H. Hultborn,et al.  Spinal control of locomotion – from cat to man , 2007, Acta physiologica.

[41]  A Prochazka,et al.  Intraspinal microstimulation excites multisegmental sensory afferents at lower stimulus levels than local alpha-motoneuron responses. , 2006, Journal of neurophysiology.

[42]  W. G. Spiller,et al.  THE TREATMENT OF PERSISTENT PAIN OF ORGANIC ORIGIN IN THE LOWER PART OF THE BODY BY DIVISION OF THE ANTEROLATERAL COLUMN OF THE SPINAL CORD , 1912 .

[43]  Warren M. Grill,et al.  Bladder and urethral pressures evoked by microstimulation of the sacral spinal cord in cats , 1999, Brain Research.

[44]  B. Renshaw.  ACTIVITY IN THE SIMPLEST SPINAL REFLEX PATHWAYS , 1940 .

[45]  J Holsheimer,et al.  Morphometry of human superficial dorsal and dorsolateral column fibres: significance to spinal cord stimulation. , 2002, Brain : a journal of neurology.

[46]  M. Fehlings,et al.  Effect of a direct current field on axons after experimental spinal cord injury. , 1989, Canadian journal of surgery. Journal canadien de chirurgie.

[47]  G. Barolat,et al.  Effects of spinal cord stimulation on spasticity and spasms secondary to myelopathy. , 1988, Applied neurophysiology.

[48]  M. Dimitrijevic,et al.  Peripheral and Central Afferent Input to the Lumbar Cord , 2005 .

[49]  R. Herman,et al.  Modulation effects of epidural spinal cord stimulation on muscle activities during walking , 2006, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[50]  J. Cook,et al.  Effects of applied electric fields on clinical cases of complete paraplegia in dogs. , 1993, Restorative neurology and neuroscience.

[51]  M. Dimitrijevic,et al.  Epidural electric stimulation of posterior structures of the human lumbar spinal cord: 1. muscle twitches – a functional method to define the site of stimulation , 2000, Spinal Cord.

[52]  Therapeutic electrical stimulation for spasticity: quantitative gait analysis. , 1998, American journal of physical medicine & rehabilitation.

[53]  B S Nashold,et al.  Electrical stimulation of the conus medullaris to control the bladder in the paraplegic patient. A 10-year review. , 1981, Applied neurophysiology.

[54]  T. Sinkjaer,et al.  Treatment of spasticity with repetitive magnetic stimulation; a double-blind placebo-controlled study , 1996, Multiple sclerosis.

[55]  R B Borgens,et al.  Enhanced spinal cord regeneration in lamprey by applied electric fields. , 1981, Science.

[56]  L. Mendell,et al.  Functional Organization of Motoneuron Pool and its Inputs , 2011 .

[57]  C H Tator,et al.  Dose-response study of the pathological effects of chronically applied direct current stimulation on the normal rat spinal cord. , 1993, Journal of neurosurgery.

[58]  Winfried Mayr,et al.  Neuromodulation of lower limb motor control in restorative neurology , 2012, Clinical Neurology and Neurosurgery.

[59]  Frank Rattay,et al.  Frequency-dependent selection of alternative spinal pathways with common periodic sensory input , 2004, Biological Cybernetics.

[60]  R. Richardson,et al.  Percutaneous epidural neurostimulation for paraplegic spasticity. , 1978, Surgical neurology.

[61]  S. Grillner,et al.  On the central generation of locomotion in the low spinal cat , 1979, Experimental Brain Research.

[62]  M. Beato,et al.  Alternating rhythmic activity induced by dorsal root stimulation in the neonatal rat spinal cord in vitro , 2001, The Journal of physiology.

[63]  G. Barolat.  Surgical management of spasticity and spasms in spinal cord injury: an overview. , 1988, The Journal of The American Paraplegia Society.

[64]  A. Prochazka,et al.  Spinal Cord Microstimulation Generates Functional Limb Movements in Chronically Implanted Cats , 2000, Experimental Neurology.

[65]  M R Dimitrijevic,et al.  Spinal cord stimulation as a tool for physiological research. , 1983, Applied neurophysiology.

[66]  F. Plum.  Handbook of Physiology. , 1960 .

[67]  V. Mushahwar,et al.  Intraspinal microstimulation preferentially recruits fatigue‐resistant muscle fibres and generates gradual force in rat , 2005, The Journal of physiology.

[68]  Á. Pascual-Leone,et al.  Reduction of Spasticity With Repetitive Transcranial Magnetic Stimulation in Patients With Spinal Cord Injury , 2010, Neurorehabilitation and neural repair.

[69]  E. Jankowska.  Interneuronal relay in spinal pathways from proprioceptors , 1992, Progress in Neurobiology.

[70]  A. Blight,et al.  Transected dorsal column axons within the guinea pig spinal cord regenerate in the presence of an applied electric field , 1986, The Journal of comparative neurology.

[71]  E. Garcia-Rill,et al.  Spinal cord stimulation-induced locomotion in the adult cat , 1992, Brain Research Bulletin.

[72]  L. Bullara,et al.  Arrays for chronic functional microstimulation of the lumbosacral spinal cord , 2004, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[73]  W J SHARRARD,et al.  The distribution of the permanent paralysis in the lower limb in poliomyelitis; a clinical and pathological study. , 1955, The Journal of bone and joint surgery. British volume.

[74]  R. Herman,et al.  Spinal cord stimulation facilitates functional walking in a chronic, incomplete spinal cord injured , 2002, Spinal Cord.

[75]  Charles Tator,et al.  Recovery of spinal cord function induced by direct current stimulation of the injured rat spinal cord. , 1987, Neurosurgery.

[76]  R B Borgens,et al.  Behavioral recovery induced by applied electric fields after spinal cord hemisection in guinea pig. , 1987, Science.

[77]  V. Edgerton,et al.  Epidural stimulation: Comparison of the spinal circuits that generate and control locomotion in rats, cats and humans , 2008, Experimental Neurology.

[78]  Warren M. Grill,et al.  Selective Microstimulation of Central Nervous System Neurons , 2000, Annals of Biomedical Engineering.

[79]  M. van Kleef,et al.  The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: Two years' follow‐up of the randomized controlled trial , 2004, Annals of neurology.

[80]  J. Schmitt,et al.  Epidural spinal cord stimulation for the control of spasticity in spinal cord injury patients lacks long-term efficacy and is not cost-effective , 1998, Spinal Cord.

[81]  V. Vanderhorst,et al.  Organization of lumbosacral motoneuronal cell groups innervating hindlimb, pelvic floor, and axial muscles in the cat , 1997, The Journal of comparative neurology.

[82]  Igor A. Lavrov,et al.  Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats , 2008, The Journal of Neuroscience.

[83]  S. McCartney,et al.  Management of chronic severe pain: cerebral neuromodulatory and neuroablative approaches. , 2007, Acta neurochirurgica. Supplement.

[84]  Cook Aw,et al.  Chronic dorsal column stimulation in multiple sclerosis. Preliminary report. , 1973 .

[85]  M. Dimitrijevic,et al.  Modification of reflex responses to lumbar posterior root stimulation by motor tasks in healthy subjects. , 2008, Artificial organs.

[86]  M. Dimitrijevic,et al.  Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 3. Control of spasticity , 2000, Spinal Cord.

[87]  C. McCaig.  Spinal neurite reabsorption and regrowth in vitro depend on the polarity of an applied electric field. , 1987, Development.

[88]  B S Nashold,et al.  Electrical activation of micturition by spinal cord stimulation. , 1971, The Journal of surgical research.

[89]  V. Mushahwar,et al.  Strategies for Generating Prolonged Functional Standing Using Intramuscular Stimulation or Intraspinal Microstimulation , 2007, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[90]  K W Horch,et al.  Muscle recruitment through electrical stimulation of the lumbo-sacral spinal cord. , 2000, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[91]  J. Oakley,et al.  High frequency cervical epidural stimulation for spasticity. , 1982, Applied Neurophysiology.

[92]  L. Vinay,et al.  Strategies to restore motor functions after spinal cord injury , 2009, Current Opinion in Neurobiology.

[93]  Hui Zhong,et al.  Facilitation of Stepping with Epidural Stimulation in Spinal Rats: Role of Sensory Input , 2008, The Journal of Neuroscience.

[94]  Charles Tator.  Phase 1 trial of oscillating field stimulation for complete spinal cord injury in humans. , 2005, Journal of neurosurgery. Spine.

[95]  S. Rossignol,et al.  Characteristics and mechanisms of locomotion induced by intraspinal microstimulation and dorsal root stimulation in spinal cats. , 2007, Journal of neurophysiology.

[96]  F Rattay,et al.  Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 2. quantitative analysis by computer modeling , 2000, Spinal Cord.

[97]  E. Jankowska,et al.  An electrophysiological demonstration of the axonal projections of single spinal interneurones in the cat , 1972, The Journal of physiology.

[98]  A. Blight,et al.  Axonal regeneration in spinal cord injury: A perspective and new technique , 1986, The Journal of comparative neurology.

[99]  S. Dixon,et al.  A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial. , 2009, Health technology assessment.

[100]  G. Romanes,et al.  The motor cell columns of the lumbo‐sacral spinal cord of the cat , 1951, The Journal of comparative neurology.

[101]  V. Mushahwar,et al.  Proposed specifications for a lumbar spinal cord electrode array for control of lower extremities in paraplegia. , 1997, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[102]  P. Wall,et al.  Pain mechanisms: a new theory. , 1965, Science.

[103]  M. Dimitrijevic,et al.  Motor control after spinal cord injury: Assessment using surface EMG , 1996, Muscle & nerve.

[104]  O. A. Nikitin,et al.  Control of Locomotor Activity in Humans and Animals in the Absence of Supraspinal Influences , 2002, Neuroscience and Behavioral Physiology.

[105]  J. González-Darder,et al.  Spinal cord stimulation in peripheral arterial disease. A cooperative study. , 1986, Journal of neurosurgery.

[106]  D. P. Lloyd.  REFLEX ACTION IN RELATION TO PATTERN AND PERIPHERAL SOURCE OF AFFERENT STIMULATION , 1943 .

[107]  A. Hicks,et al.  Spasticity after spinal cord injury , 2005, Spinal Cord.

[108]  R B Borgens,et al.  An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs. , 1999, Journal of neurotrauma.

[109]  A Curt,et al.  From spinal shock to spasticity , 2000, Neurology.