- Email: [email protected]
Restorative neurology: Past, present, and future
Clinical Neurology and Neurosurgery 114 (2012) 524–527
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Restorative neurology: Past, present, and future Justin M. Brown, Byron A. Kakulas ∗
1. Introduction To fully appreciate the spectacular progress in individualized neurophysiologically based functional enhancement represented by Restorative Neurology (RN) there is nothing more compelling than to view the new discipline in historical perspective. In contrast to the in depth knowledge and sophisticated techniques underpinning RN as shown in the preceding articles, remarkably, it is only in comparatively recent times that neurophysiologists were absorbed with learning how an action potential was transmitted in the giant axon of the squid. Modern neurophysiology began with Sir Charles Sherrington in the early years of the 20th century. Sherrington addressed the question posed by the early morphologists as to whether the brain was reticular in structure (Golgi’s paradigm) or consisted of distinct cells – the neuron doctrine (Cajal’s thesis). Sherrington’s experiments confirmed Cajal’s view. Sherrington is also well known for his concept of signal “convergence and integration” resulting in a “final common pathway” [1]. While Camillo Golgi and Santiago Ramon y Cajal shared the Nobel Prize in 1906 in recognition of their work on the structure of the nervous system, Sherrington was awarded the Nobel Prize in 1932 along with Edgar Adrian “for their discoveries regarding the functions of neurons”. Another major step forward came with Hodgkin and Huxley’s experiments on signal transmission. They found the propagation of the action potential resulted from the exchange of sodium and potassium ions across the axonal membrane. They were awarded the Nobel Prize together with Sir John Eccles in 1963 for their discoveries of these ionic mechanisms. Eccles settled the controversy as to whether the synapse was chemical or electrical in nature. He showed that in fact it was (most often) chemical and as we now know there are many neurotransmitters recognised [2]. Contemporaneous to the above, a degree of insight into the functional anatomy of the human brain was gained by a system of clinico-pathological correlation (CPC). In this respect two neurologists of great stature, Raymond D Adams and Derek Denny Brown both at Harvard Medical School in the 1950s and 1960s deserve mention. Neurological functions lost in life were compared to the changes found in the brain at necropsy. In this way centers for speech, sight, voluntary movement, and sensation came to be rec-
∗ Corresponding author. E-mail address: [email protected] (B.A. Kakulas). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2012.02.055
ognized. Because knowledge gained in this way depended upon a system of “negatives” it was very limiting and quite the opposite to neurophysiology, which is positive in nature. Other milestones in the history of human neurophysiology were the development of diagnostic Electro-Encephalography (EEG) by Berger in1924 [3] evolving from the discovery of brain waves by Caton in1875 and Moruzzi and Magoun’s concepts of a brain stem “reticular activating system” in 1949. Electromyography has a longer history beginning as early as the 17th century with the observation of muscle contraction on electrical stimulation by Redi in 1666. However clinical electromyography (EMG) did not emerge until the 1960’s. Further significant progress in clinical neurophysiology of muscle and nerve may be ascribed to Erik Kugelberg, Fritz Buchtal, and Peter Dyck among others. 2. The foundation restorative neurology Building upon these neurophysiological tools, between 1967 and 1973 Milan Dimitrijevic and Peter Nathan undertook a series of experiments to elucidate the principles of spasticity in man by developing what appears to be the first multichannel dynamic surface EMG system [4–8]. This set of studies provided the basis for what has since evolved into the clinical practice of restorative neurology, providing both an understanding of aspects of degraded motor control and a methodology for characterizing this. In 1982, Dimitrijevic held a Symposium on Restorative Neurology where was gathered a number of pioneers in the field of human motor control. Together with Sir John Eccles, he compiled a series of books entitled “Recent Achievements in Restorative Neurology” and established an important approach to the recovery of function following neurological injury. It is in honor of the career of Professor Milan R Dimitrijevic that these Proceedings are dedicated. Restorative neurology arose as a distinct discipline in the late 20th century from Professor Dimitrijevic’s general interest in human neurophysiology and in particular the study of spinal cord injury (SCI). His early investigations revealed residual activity in the clinically “motor complete” spinal cord injured patients that could be modified toward improving the functional status. By identifying this “discomplete syndrome,” unwanted reflexes (spasms) could be suppressed and residual voluntary control unmasked, based on the particular neurophysiological profile of a given patient. Thus the new discipline of RN offered a complementary set of tools to those available as part of conventional rehabilitation. Dr. Dimitrijevic soon established a research team composed of
J.M. Brown, B.A. Kakulas / Clinical Neurology and Neurosurgery 114 (2012) 524–527
neurologists, neurosurgeons, neurophysiologists, physiatrists and engineers under the auspices of the Vivian L. Smith Foundation for Restorative Neurology in Houston and the subsequently established Division of Restorative Neurology and Human Neurobiology at Baylor College of Medicine. Their investigations resulted in rapid progress in the understanding of normal and disordered human motor control, which was quickly translated to the clinic. Dr. Dimitrijevic’s work attracted international attention and a strong following developed as shown in this issue. There is no better way to describe the concept and practice of RN and its approach to clinical functional enhancement than to quote from its founder, Milan Dimitrijevic, who states that “rather than focusing on the deficits and lost function caused by upper motor neuron lesions or disorders, it is more advantageous to elucidate, in each individual, the specific neural functions that remain available, and then, to build upon them by designing a treatment protocol to optimize their effectiveness and thus improve recovery.” He asserts that one of the primary goals of RN is to modify spinal cord network activation, which may be achieved by applying electrical stimulation to activate cutaneous afferents, peripheral nerves, posterior roots or even posterior columns of the spinal cord in order to maintain an adequate central state of excitability. When maintained at an adequate level, the spinal cord network is better able to generate responses to appropriate input and thereby produce a functional motor output. Ideally, complete reconstruction of the affected part of the CNS to restore the original anatomy and physiology would be the ultimate intervention to achieve the best outcome for the patient. That is, eliminating the lesion and regenerating the anatomy with re-programming the neuronal/synaptic network to follow. Realistically this may never be a feasible endeavour. We are left with the second approach, which is to modify and modulate residual functions, guiding plasticity and augmenting the nervous systems ability to activate latent circuits. This special issue of the Clinical Neurology and Neurosurgery provides the information as to how it could best be applied to restoring motor function to individuals with CNS impairment. Once the neurophysiological profiling is established, the techniques of RN consist of physical, electrical, pharmacological, biological and surgical methodologies. An important sampling of RN theory, assessments and interventions are illustrated in the articles of this volume.
3. Highlights of the articles It may be seen from this special Issue of Clinical Neurology and Neurosurgery that the state of the art in RN is wide ranging. Each of the authors is an internationally recognised authority possessing great expertise in their specialty. Those specialties represented in this group include clinical neurology, neurophysiology, neuroradiology, neuroscience, neurosurgery, developmental neurology, physical therapy, neuropathology, engineering and neurorehabilitation. The authors are drawn from several continents, which also speaks for the value of the discipline with each group collaborating with, and guided by the master Professor Milan R. Dimitrijevic. The articles demonstrate the extraordinary diversity of interventions which make up RN and the reader is referred to these for more information. In the introduction Dimitrijevic provides a comprehensive description of RN, beginning with elucidating the basic characteristics of the nervous system – conducting and processing – and how these processes contribute to the motor programs which are expressed as programs such as posture and locomotion. He then reviews the concepts of assessment and modalities of intervention, using epidural stimulation as an important illustration. In his paper on motor control John Rothwell highlights the change in our understanding of CNS function leading away from the
525
concept of serial planning and heading toward the idea of parallel processing. Rothwell emphasises that the system works as a whole and that the spinal cord is not bound by specific pathways but manifests great adaptability and plasticity so that parallel and divergent projection of descending inputs mainly to spinal interneurons gives an abundance of connections that must be selected to produce the required [motor] outputs “The robustness in such a design is thus evident.” Thus the disordered anatomy following SCI is not necessarily a limiting factor on recovery, but may in fact provide opportunity for the application of RN. Keith Tansey, Barry McKay, and Byron Kakulas are concerned with CNS development, spatial temporal learning and disconnection as a consequence of injury. They discuss the enormous complexity of the nervous system and comment upon two approaches with regard to restoration of function of the disordered “new” anatomy. Firstly there is the theoretical possibility of recreating the original system through regeneration with sprouting and the activation of silent synapses. Their second approach is more realistic beginning with an in depth assessment of the new system followed by implementation of RN interventions which capitalize upon the profile of residual capacity as determined by these investigations. It is the assessment of residual functions which is one of the unique aspects of RN when compared with contemporary rehabilitation. The following set of communications provide methods by which this can be accomplished. Summarizing the work of Professor Dimitrijevic, Justin Brown and Keith Tansey provide a thorough discussion of clinical examination techniques which allow reliable detailed characterization of residual functions from single joint volitional control, to multijoint activation, augmentation techniques, and finally to descending influence upon elicited phenomena. In the following article, Barry McKay using his extensive experience with the Brain Motor Control Assessment (BMCA) demonstrates how further characterization of these capacities using neurophysiological techniques can be achieved. He establishes the validity of this technique in comparison to more commonly employed modalities and how insights into the capacities of the nervous system can be elucidated. Janez Zidar and Natasa Bizovicar then demonstrate the utility of another neurophysiological technique which is being developed to characterize cortical involvement in the setting of amyotrophic lateral sclerosis using movement-related cortical potentials. Finally Patrick Stroman provides an excellent overview of where we are with imaging of CNS changes corresponding to inflammation, demyelination, blood flow, and axonal integrity and what lays on the horizon with advanced MRI techniques for elucidating residual capabilities of the nervous system. Justin Brown, David Deriso, and Keith Tansey then introduce the management of traumatic central nervous system injury. Brief recount of events from the intial hospitalization to traditional rehabilitation is provided while establishing the place for RN modalities and how these may augment the typical approach to these injuries. They introduce restorative concepts from physical intervention to stimulation and on to reconstructive neurosurgical options that offer additional functional gains not typically available in modern rehabilitation settings. Foreshadowing is provided for the following contributions which outline specific restorative modalities in function recovery. Karen Pape leads off the interventional discussion by first reviewing concepts which are more salient in the paediatric population but which are useful to consider even in the adult population, including masking of latent function by apraxic scenarios. She gives attention to developmental neurology in demonstrating the principles which underlie normal development compared with maladaptive neurophysiology following SCI invoking neuroplasticity as a major factor in each case. The object therefore of RN
526
J.M. Brown, B.A. Kakulas / Clinical Neurology and Neurosurgery 114 (2012) 524–527
being to influence the property of plasticity for recovery employing various methodologies including the “use it or lose it” closed loop EMG triggered stimulation training system. Dr. Pape also presents the role of threshold electrical stimulation in enhancing functional recruitment of otherwise latent musculature. Mary Galea describes the benefits of the biophysical modalities including physical therapy with techniques which optimize recovery and minimize disability. She reviews historical approaches and how the emphasis has changed in recent years to an emphasis on active, task-related purposeful rehabilitation. She advocates for further investigation into some of the techniques that were previously used which may still have merit and studies which would better elucidate ideal timing and dosing of these interventions. Karen Minassian, Ursula Hofstoetter, Keith Tansey, and Winfried Mayr next provide an informative account of neuromodulation as a tool in RN. They briefly review common applications of focal FES interventions and then move on to the great restorative potential of epidural stimulation, a modality that demonstrates an essential RN concept of activating critical latent circuits to restore motor control. The wide range of improvements which can be obtained these modalities are described in detail. Simon Tang and colleagues then discuss their experience with using an RN approach to the application of Botulinum toxin in patients with spastic equinovarus gait. They not only demonstrate improved function in these patients but neurophysiological methods reveal restoration of function in dorsiflexor muscles in a large subset. Similarly Matthew Kauffman and colleagues describe their experience with recovering diaphragmatic function by surgically eliminating a source of compressive ischemic neurapraxia – again allowing activation of latent but present functional capacity. Justin Brown, Nicholas Vivio, and Geoffrey Sheean then provide a comprehensive discussion of the reconstructive neurosurgery approach to paralysis from three major sources: peripheral nerve injury, spinal cord injury, and finally brain injury. The concepts of tendon transfer, nerve reconstruction and nerve transfer are developed in their application to each of these conditions. Redistribution of well-cortically controlled neural input to critical effectors is emphasized as well as elimination of pathological activation which can mask underlying capabilities. The critical role of neurophysiology is described in detail in its role in directing these procedures. Finally, in considering the future of RN John Martin describes how advances in neurophysiology and neurobiology will contribute through relearning and by facilitating the use of a multiplicity of non-pyramidal motor systems. Emerging restorative strategies involving accessing motor functions which reside within the spinal cord, neural activity-based approaches, and emphasis is given to his depth of experience with circuit-selective activation which may promote plasticity via sprouting of spared axons.
4. Closing remarks These proceedings demonstrate the depth of knowledge and its application which underlies modern RN. Appreciation of the disordered neurophysiology of SCI is applied ingeniously toward improving the patients’ status through modulation techniques and interventions. It is to be expected that by keeping abreast of developments in the basic neurosciences, advances will be rapidly translated to RN in which case even greater benefits in neurorehabilitation will accrue, especially in the functional outcome for the SCI patient. While considering the future direction of RN it is of great importance to be aware of the underlying neuropathology in SCI in which the relationship between structure and function has been elucidated by careful clinic-pathological correlation [9]. It should be kept in mind that the natural history post injury is
Fig. 1. “End stage” mid cervical spinal cord in cross section many years after injury showing multilocular cavities traversed by glial bundles and a small amount of residual white matter at the periphery. Macroscopic view.
dynamic, so that its clinical expression is subject to continuous change. There is advancing Wallerian degeneration of long tracts with trans-synaptic neuronal degeneration, gliosis, and plastic changes at a microscopic level. How much sprouting and new synaptic connections may occur spontaneously is not revealed anatomically, although there is neurophysiological evidence of its occurrence. The continuously evolving post injury status of structure and function gives emphasis to the first step in RN being full clinical and physiological assessment to inventory remaining capacities as they exist at that point in time. Paramount in consideration of the future potential of RN is the seminal neuropathological finding that in the majority of SCI injuries there is continuity of greater or lesser amounts of white matter across the lesion site regardless of whether the patient was clinically motor incomplete or motor complete. The term anatomically discomplete is applicable to those cases in which all function is lost below the level of injury, but in whom surviving white matter can be found traversing the lesion. In life these patients have neurophysiological evidence of signal transmission through the injury site i.e. the clinical discomplete syndrome [10] (Fig. 1). The importance of the surviving axons lies in the fact that they provide the framework for repair and future reconstruction. In this regard it is noteworthy that clinico-pathological quantification indicates that only a small proportion of surviving long tract axons is required for maintenance of function [11]. Thus the axons that have escaped injury are available for potential restorative measures in SCI. The residual axons which have survived the injury may be augmented and modulated through plasticity to be of clinical value or they can provide the framework for regeneration e.g. through new sprouts and branching to be later modulated and reprogrammed physiologically (Fig. 2). Such optimism rests on the fact that structural/functional relationships are not rigid in the CNS. Given a certain amount of surviving neural tissue, no matter what its origin may have been, it may be re-educated to perform a different function. In this way plasticity directed by modulation may be of much of benefit in RN. To sum up it may be assumed that all of the methods described at this conference will continue to grow and rapidly evolve in the future RN treatments are in no way restricted to standard techniques but encompass all progress in neuroscience Thus it may be expected that neurophysiological methods will become more sophisticated. New biological agents such and trophic factors will be discovered and genetic modification will become more applicable. Pharmacological agents will widen while grafts and transplants will be improved. Regeneration and reconstruction will become more feasible as advances in stem cell technology occur. Eventually the spinal cord will be fully repaired anatomically. The challenge
J.M. Brown, B.A. Kakulas / Clinical Neurology and Neurosurgery 114 (2012) 524–527
527
benefit of those patients now affected by SCI or stroke and other chronic neurological disorders. Regrettably much of RN is still not well known outside of the discipline even though RN has much to offer conventional neurorehabilitation. Therefore a most desirable outcome of this publication and the scientific sessions it represents would be for their wide adoption. A new textbook devoted to RN recently published by Oxford University Press will do much to promote this cause [12]. References
Fig. 2. Similar to Fig. 1. Cross section stained for myelin depicting residual white matter at the periphery which has survived the injury (stained black). Loyez method, macroscopic view.
will then be to restore normal neurophysiological function by training and re-education so that reflexes volition motor control posture and tone sensation autonomic and all other neural functions return to normal. Hand in hand with these advances in neuroscience will be the growth of the clinical methods of RN such as electrical and magnetic stimulation advances in reconstructive neurosurgery and the medical ancillaries of orthotics and physical therapy. Also to be anticipated are improved prostheses and robotics. Thus there is almost unlimited potential for the development of RN through further research. As a final word it should be stated that the established methods of RN as described above need to be more widely adopted for the
[1] Sherrington CS. The integrative activity of the nervous system. New Haven: Yale Univ. Press; 1906. [2] Eccles JC. The physiology of synapses. New York: Academic Press; 1964. [3] Berger H, Gloor P. Hans Berger on the electroencephalogram of man. The fourteen original reports on the human electroencephalogram. Gloor Electroenceph Clin Neurophysiol Suppl 1969:28. [4] Dimitrijevic MR, Nathan PW. Studies of spasticity in man. I. Some features of spasticity. Brain 1967;90:1–30. [5] Dimitrijevic MR, Nathan PW. Studies of spasticity in man. 3. Analysis of revlex activity evoked by noxious cutaneous stimulation. Brain 1968;91:349– 68. [6] Dimitrijevic MR, Nathan PW. Studies of spasticity in man. 4. Changes in flexion reflex with repetitive cutaneous stimulation in spinal man. Brain 1970;93:743–68. [7] Dimitrijevic MR, Nathan PW. Studies of spasticity in man. 5. Dishabituation of the flexion reflex in spinal man. Brain 1971;94:77–90. [8] Dimitrijevic MR, Nathan PW. Studies of spasticity in man. 6. Habituation, dishabituation and sensitization of tenson reflexes in spinal man. Brain 1973;96:337–54. [9] Kakulas BA. Neuropathology: the foundation for new treatments in spinal cord injury. Spinal Cord 2004;42:549–63. [10] Sherwood AM, Dimitrijevic MR, McKay WB. Evidence of subclinical brain influence in clinically complete spinal cord injury: discomplete SCI. J Neurol Sci 1992;110:90–8. [11] Kakulas BA. Neuropathology of human spinal cord injury: the basis for new treatments. Am J Neuroprot Neuroregener 2009;1:11–21. [12] Dimitrijevic MR, Kakulas BA, McKay WB, Vrbova G. Restorative neurology of spinal cord injury. New York: Oxford University Press; 2012.
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Restorative neurology: Past, present, and future Justin M. Brown, Byron A. Kakulas ∗
1. Introduction To fully appreciate the spectacular progress in individualized neurophysiologically based functional enhancement represented by Restorative Neurology (RN) there is nothing more compelling than to view the new discipline in historical perspective. In contrast to the in depth knowledge and sophisticated techniques underpinning RN as shown in the preceding articles, remarkably, it is only in comparatively recent times that neurophysiologists were absorbed with learning how an action potential was transmitted in the giant axon of the squid. Modern neurophysiology began with Sir Charles Sherrington in the early years of the 20th century. Sherrington addressed the question posed by the early morphologists as to whether the brain was reticular in structure (Golgi’s paradigm) or consisted of distinct cells – the neuron doctrine (Cajal’s thesis). Sherrington’s experiments confirmed Cajal’s view. Sherrington is also well known for his concept of signal “convergence and integration” resulting in a “final common pathway” [1]. While Camillo Golgi and Santiago Ramon y Cajal shared the Nobel Prize in 1906 in recognition of their work on the structure of the nervous system, Sherrington was awarded the Nobel Prize in 1932 along with Edgar Adrian “for their discoveries regarding the functions of neurons”. Another major step forward came with Hodgkin and Huxley’s experiments on signal transmission. They found the propagation of the action potential resulted from the exchange of sodium and potassium ions across the axonal membrane. They were awarded the Nobel Prize together with Sir John Eccles in 1963 for their discoveries of these ionic mechanisms. Eccles settled the controversy as to whether the synapse was chemical or electrical in nature. He showed that in fact it was (most often) chemical and as we now know there are many neurotransmitters recognised [2]. Contemporaneous to the above, a degree of insight into the functional anatomy of the human brain was gained by a system of clinico-pathological correlation (CPC). In this respect two neurologists of great stature, Raymond D Adams and Derek Denny Brown both at Harvard Medical School in the 1950s and 1960s deserve mention. Neurological functions lost in life were compared to the changes found in the brain at necropsy. In this way centers for speech, sight, voluntary movement, and sensation came to be rec-
∗ Corresponding author. E-mail address: [email protected] (B.A. Kakulas). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2012.02.055
ognized. Because knowledge gained in this way depended upon a system of “negatives” it was very limiting and quite the opposite to neurophysiology, which is positive in nature. Other milestones in the history of human neurophysiology were the development of diagnostic Electro-Encephalography (EEG) by Berger in1924 [3] evolving from the discovery of brain waves by Caton in1875 and Moruzzi and Magoun’s concepts of a brain stem “reticular activating system” in 1949. Electromyography has a longer history beginning as early as the 17th century with the observation of muscle contraction on electrical stimulation by Redi in 1666. However clinical electromyography (EMG) did not emerge until the 1960’s. Further significant progress in clinical neurophysiology of muscle and nerve may be ascribed to Erik Kugelberg, Fritz Buchtal, and Peter Dyck among others. 2. The foundation restorative neurology Building upon these neurophysiological tools, between 1967 and 1973 Milan Dimitrijevic and Peter Nathan undertook a series of experiments to elucidate the principles of spasticity in man by developing what appears to be the first multichannel dynamic surface EMG system [4–8]. This set of studies provided the basis for what has since evolved into the clinical practice of restorative neurology, providing both an understanding of aspects of degraded motor control and a methodology for characterizing this. In 1982, Dimitrijevic held a Symposium on Restorative Neurology where was gathered a number of pioneers in the field of human motor control. Together with Sir John Eccles, he compiled a series of books entitled “Recent Achievements in Restorative Neurology” and established an important approach to the recovery of function following neurological injury. It is in honor of the career of Professor Milan R Dimitrijevic that these Proceedings are dedicated. Restorative neurology arose as a distinct discipline in the late 20th century from Professor Dimitrijevic’s general interest in human neurophysiology and in particular the study of spinal cord injury (SCI). His early investigations revealed residual activity in the clinically “motor complete” spinal cord injured patients that could be modified toward improving the functional status. By identifying this “discomplete syndrome,” unwanted reflexes (spasms) could be suppressed and residual voluntary control unmasked, based on the particular neurophysiological profile of a given patient. Thus the new discipline of RN offered a complementary set of tools to those available as part of conventional rehabilitation. Dr. Dimitrijevic soon established a research team composed of
J.M. Brown, B.A. Kakulas / Clinical Neurology and Neurosurgery 114 (2012) 524–527
neurologists, neurosurgeons, neurophysiologists, physiatrists and engineers under the auspices of the Vivian L. Smith Foundation for Restorative Neurology in Houston and the subsequently established Division of Restorative Neurology and Human Neurobiology at Baylor College of Medicine. Their investigations resulted in rapid progress in the understanding of normal and disordered human motor control, which was quickly translated to the clinic. Dr. Dimitrijevic’s work attracted international attention and a strong following developed as shown in this issue. There is no better way to describe the concept and practice of RN and its approach to clinical functional enhancement than to quote from its founder, Milan Dimitrijevic, who states that “rather than focusing on the deficits and lost function caused by upper motor neuron lesions or disorders, it is more advantageous to elucidate, in each individual, the specific neural functions that remain available, and then, to build upon them by designing a treatment protocol to optimize their effectiveness and thus improve recovery.” He asserts that one of the primary goals of RN is to modify spinal cord network activation, which may be achieved by applying electrical stimulation to activate cutaneous afferents, peripheral nerves, posterior roots or even posterior columns of the spinal cord in order to maintain an adequate central state of excitability. When maintained at an adequate level, the spinal cord network is better able to generate responses to appropriate input and thereby produce a functional motor output. Ideally, complete reconstruction of the affected part of the CNS to restore the original anatomy and physiology would be the ultimate intervention to achieve the best outcome for the patient. That is, eliminating the lesion and regenerating the anatomy with re-programming the neuronal/synaptic network to follow. Realistically this may never be a feasible endeavour. We are left with the second approach, which is to modify and modulate residual functions, guiding plasticity and augmenting the nervous systems ability to activate latent circuits. This special issue of the Clinical Neurology and Neurosurgery provides the information as to how it could best be applied to restoring motor function to individuals with CNS impairment. Once the neurophysiological profiling is established, the techniques of RN consist of physical, electrical, pharmacological, biological and surgical methodologies. An important sampling of RN theory, assessments and interventions are illustrated in the articles of this volume.
3. Highlights of the articles It may be seen from this special Issue of Clinical Neurology and Neurosurgery that the state of the art in RN is wide ranging. Each of the authors is an internationally recognised authority possessing great expertise in their specialty. Those specialties represented in this group include clinical neurology, neurophysiology, neuroradiology, neuroscience, neurosurgery, developmental neurology, physical therapy, neuropathology, engineering and neurorehabilitation. The authors are drawn from several continents, which also speaks for the value of the discipline with each group collaborating with, and guided by the master Professor Milan R. Dimitrijevic. The articles demonstrate the extraordinary diversity of interventions which make up RN and the reader is referred to these for more information. In the introduction Dimitrijevic provides a comprehensive description of RN, beginning with elucidating the basic characteristics of the nervous system – conducting and processing – and how these processes contribute to the motor programs which are expressed as programs such as posture and locomotion. He then reviews the concepts of assessment and modalities of intervention, using epidural stimulation as an important illustration. In his paper on motor control John Rothwell highlights the change in our understanding of CNS function leading away from the
525
concept of serial planning and heading toward the idea of parallel processing. Rothwell emphasises that the system works as a whole and that the spinal cord is not bound by specific pathways but manifests great adaptability and plasticity so that parallel and divergent projection of descending inputs mainly to spinal interneurons gives an abundance of connections that must be selected to produce the required [motor] outputs “The robustness in such a design is thus evident.” Thus the disordered anatomy following SCI is not necessarily a limiting factor on recovery, but may in fact provide opportunity for the application of RN. Keith Tansey, Barry McKay, and Byron Kakulas are concerned with CNS development, spatial temporal learning and disconnection as a consequence of injury. They discuss the enormous complexity of the nervous system and comment upon two approaches with regard to restoration of function of the disordered “new” anatomy. Firstly there is the theoretical possibility of recreating the original system through regeneration with sprouting and the activation of silent synapses. Their second approach is more realistic beginning with an in depth assessment of the new system followed by implementation of RN interventions which capitalize upon the profile of residual capacity as determined by these investigations. It is the assessment of residual functions which is one of the unique aspects of RN when compared with contemporary rehabilitation. The following set of communications provide methods by which this can be accomplished. Summarizing the work of Professor Dimitrijevic, Justin Brown and Keith Tansey provide a thorough discussion of clinical examination techniques which allow reliable detailed characterization of residual functions from single joint volitional control, to multijoint activation, augmentation techniques, and finally to descending influence upon elicited phenomena. In the following article, Barry McKay using his extensive experience with the Brain Motor Control Assessment (BMCA) demonstrates how further characterization of these capacities using neurophysiological techniques can be achieved. He establishes the validity of this technique in comparison to more commonly employed modalities and how insights into the capacities of the nervous system can be elucidated. Janez Zidar and Natasa Bizovicar then demonstrate the utility of another neurophysiological technique which is being developed to characterize cortical involvement in the setting of amyotrophic lateral sclerosis using movement-related cortical potentials. Finally Patrick Stroman provides an excellent overview of where we are with imaging of CNS changes corresponding to inflammation, demyelination, blood flow, and axonal integrity and what lays on the horizon with advanced MRI techniques for elucidating residual capabilities of the nervous system. Justin Brown, David Deriso, and Keith Tansey then introduce the management of traumatic central nervous system injury. Brief recount of events from the intial hospitalization to traditional rehabilitation is provided while establishing the place for RN modalities and how these may augment the typical approach to these injuries. They introduce restorative concepts from physical intervention to stimulation and on to reconstructive neurosurgical options that offer additional functional gains not typically available in modern rehabilitation settings. Foreshadowing is provided for the following contributions which outline specific restorative modalities in function recovery. Karen Pape leads off the interventional discussion by first reviewing concepts which are more salient in the paediatric population but which are useful to consider even in the adult population, including masking of latent function by apraxic scenarios. She gives attention to developmental neurology in demonstrating the principles which underlie normal development compared with maladaptive neurophysiology following SCI invoking neuroplasticity as a major factor in each case. The object therefore of RN
526
J.M. Brown, B.A. Kakulas / Clinical Neurology and Neurosurgery 114 (2012) 524–527
being to influence the property of plasticity for recovery employing various methodologies including the “use it or lose it” closed loop EMG triggered stimulation training system. Dr. Pape also presents the role of threshold electrical stimulation in enhancing functional recruitment of otherwise latent musculature. Mary Galea describes the benefits of the biophysical modalities including physical therapy with techniques which optimize recovery and minimize disability. She reviews historical approaches and how the emphasis has changed in recent years to an emphasis on active, task-related purposeful rehabilitation. She advocates for further investigation into some of the techniques that were previously used which may still have merit and studies which would better elucidate ideal timing and dosing of these interventions. Karen Minassian, Ursula Hofstoetter, Keith Tansey, and Winfried Mayr next provide an informative account of neuromodulation as a tool in RN. They briefly review common applications of focal FES interventions and then move on to the great restorative potential of epidural stimulation, a modality that demonstrates an essential RN concept of activating critical latent circuits to restore motor control. The wide range of improvements which can be obtained these modalities are described in detail. Simon Tang and colleagues then discuss their experience with using an RN approach to the application of Botulinum toxin in patients with spastic equinovarus gait. They not only demonstrate improved function in these patients but neurophysiological methods reveal restoration of function in dorsiflexor muscles in a large subset. Similarly Matthew Kauffman and colleagues describe their experience with recovering diaphragmatic function by surgically eliminating a source of compressive ischemic neurapraxia – again allowing activation of latent but present functional capacity. Justin Brown, Nicholas Vivio, and Geoffrey Sheean then provide a comprehensive discussion of the reconstructive neurosurgery approach to paralysis from three major sources: peripheral nerve injury, spinal cord injury, and finally brain injury. The concepts of tendon transfer, nerve reconstruction and nerve transfer are developed in their application to each of these conditions. Redistribution of well-cortically controlled neural input to critical effectors is emphasized as well as elimination of pathological activation which can mask underlying capabilities. The critical role of neurophysiology is described in detail in its role in directing these procedures. Finally, in considering the future of RN John Martin describes how advances in neurophysiology and neurobiology will contribute through relearning and by facilitating the use of a multiplicity of non-pyramidal motor systems. Emerging restorative strategies involving accessing motor functions which reside within the spinal cord, neural activity-based approaches, and emphasis is given to his depth of experience with circuit-selective activation which may promote plasticity via sprouting of spared axons.
4. Closing remarks These proceedings demonstrate the depth of knowledge and its application which underlies modern RN. Appreciation of the disordered neurophysiology of SCI is applied ingeniously toward improving the patients’ status through modulation techniques and interventions. It is to be expected that by keeping abreast of developments in the basic neurosciences, advances will be rapidly translated to RN in which case even greater benefits in neurorehabilitation will accrue, especially in the functional outcome for the SCI patient. While considering the future direction of RN it is of great importance to be aware of the underlying neuropathology in SCI in which the relationship between structure and function has been elucidated by careful clinic-pathological correlation [9]. It should be kept in mind that the natural history post injury is
Fig. 1. “End stage” mid cervical spinal cord in cross section many years after injury showing multilocular cavities traversed by glial bundles and a small amount of residual white matter at the periphery. Macroscopic view.
dynamic, so that its clinical expression is subject to continuous change. There is advancing Wallerian degeneration of long tracts with trans-synaptic neuronal degeneration, gliosis, and plastic changes at a microscopic level. How much sprouting and new synaptic connections may occur spontaneously is not revealed anatomically, although there is neurophysiological evidence of its occurrence. The continuously evolving post injury status of structure and function gives emphasis to the first step in RN being full clinical and physiological assessment to inventory remaining capacities as they exist at that point in time. Paramount in consideration of the future potential of RN is the seminal neuropathological finding that in the majority of SCI injuries there is continuity of greater or lesser amounts of white matter across the lesion site regardless of whether the patient was clinically motor incomplete or motor complete. The term anatomically discomplete is applicable to those cases in which all function is lost below the level of injury, but in whom surviving white matter can be found traversing the lesion. In life these patients have neurophysiological evidence of signal transmission through the injury site i.e. the clinical discomplete syndrome [10] (Fig. 1). The importance of the surviving axons lies in the fact that they provide the framework for repair and future reconstruction. In this regard it is noteworthy that clinico-pathological quantification indicates that only a small proportion of surviving long tract axons is required for maintenance of function [11]. Thus the axons that have escaped injury are available for potential restorative measures in SCI. The residual axons which have survived the injury may be augmented and modulated through plasticity to be of clinical value or they can provide the framework for regeneration e.g. through new sprouts and branching to be later modulated and reprogrammed physiologically (Fig. 2). Such optimism rests on the fact that structural/functional relationships are not rigid in the CNS. Given a certain amount of surviving neural tissue, no matter what its origin may have been, it may be re-educated to perform a different function. In this way plasticity directed by modulation may be of much of benefit in RN. To sum up it may be assumed that all of the methods described at this conference will continue to grow and rapidly evolve in the future RN treatments are in no way restricted to standard techniques but encompass all progress in neuroscience Thus it may be expected that neurophysiological methods will become more sophisticated. New biological agents such and trophic factors will be discovered and genetic modification will become more applicable. Pharmacological agents will widen while grafts and transplants will be improved. Regeneration and reconstruction will become more feasible as advances in stem cell technology occur. Eventually the spinal cord will be fully repaired anatomically. The challenge
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benefit of those patients now affected by SCI or stroke and other chronic neurological disorders. Regrettably much of RN is still not well known outside of the discipline even though RN has much to offer conventional neurorehabilitation. Therefore a most desirable outcome of this publication and the scientific sessions it represents would be for their wide adoption. A new textbook devoted to RN recently published by Oxford University Press will do much to promote this cause [12]. References
Fig. 2. Similar to Fig. 1. Cross section stained for myelin depicting residual white matter at the periphery which has survived the injury (stained black). Loyez method, macroscopic view.
will then be to restore normal neurophysiological function by training and re-education so that reflexes volition motor control posture and tone sensation autonomic and all other neural functions return to normal. Hand in hand with these advances in neuroscience will be the growth of the clinical methods of RN such as electrical and magnetic stimulation advances in reconstructive neurosurgery and the medical ancillaries of orthotics and physical therapy. Also to be anticipated are improved prostheses and robotics. Thus there is almost unlimited potential for the development of RN through further research. As a final word it should be stated that the established methods of RN as described above need to be more widely adopted for the
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