Clinical Neurophysiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
Vestibular function and vestibular evoked myogenic potentials (VEMPs) in spasticity See Article, pages xxx–xxx
In this issue of Clinical Neurophysiology, Miller et al. (2014) report changes in the cervical vestibular evoked myogenic potential (cVEMP) to short tone bursts in patients with spasticity. They have found that the responses are significantly larger on the side of paresis/spasticity and have shown a correlation between the degree of spasticity and the degree of asymmetry of the cVEMP. Based on these findings they propose a role for the vestibulospinal projections in causing spasticity. The findings are of potential significance in explaining the syndrome of spasticity which is commonly seen as a consequence of neurological disease affecting the corticospinal tracts. In passing it may be of interest that JGC’s original interest in the VEMP was as a means of assessing a nonpyramidal pathway (Colebatch et al., 1994). The vestibular apparatus is difficult to assess due to its size and location, and imaging has an important but limited role. Traditional methods were based upon assessing the vestibular-ocular reflex, particularly that arising from the horizontal canal, in response to rotation or thermal stimulation (caloric testing). The cVEMP represents the application of classical electrophysiological methods to the vestibular system, with the repetitive application of an effective stimulus and averaging of the result. Unlike most other evoked potentials, the cVEMP is generated by modulation of EMG activity and is not present without tonic activation of the target muscle (the sternocleidomastoid muscle; SCM). The pathway mediating the response to air conducted (AC) stimuli is now widely accepted to arise from irregularly firing afferents innervating the otoliths, mainly the saccule, synapsing in the ipsilateral vestibular nucleus and descending ipsilaterally via the medial vestibulospinal tract to synapse on the motoneurones of the SCM (Kushiro et al., 1999). Spasticity is a state of hyperreflexia, defined by a specific increase in muscle tone as well as tendon jerk reflexes in subjects at rest (Lance, 1980) and occurs only when lesions interrupt corticospinal fibres (Burke, 1988). The changes in muscle tone are best appreciated in the legs at the knee and show a characteristic velocity dependence (Lance, 1980). However, the syndrome is not a consequence of the corticospinal lesion per se (Burke, 1988). In humans limited and specific lesions cause only a restricted deficit, with increased tendon reflexes and the Babinski sign (Bucy et al., 1964) and in rhesus monkeys Lawrence and Kuypers (1968) sectioned the pyramidal tract at the decussation of the pyramids, also with limited deficits. They concluded that ‘‘in the absence of the corticospinal pathways, the descending subcorticospinal pathways
are capable of guiding a range of activity which includes independent limb movements in addition to total body–limb activity. The corticospinal pathways superimpose speed and agility upon these subcortical mechanisms, and, in addition, provide the capacity for a high degree of fractionation of movements as exemplified by individual finger movements.’’ Pathology rarely produces such selective lesions, and clinical observation, aided by improvements in imaging, suggests that a simple corticospinal lesion might result in tendon jerk hyperreflexia and the Babinski sign, but is unlikely to cause the typical changes in passive muscle tone. Changes in muscle tone in the legs in association with cervical myelopathy, for example, are usually not seen unless there are changes in the cord which probably extend beyond the corticospinal tracts. Better resolution of MRI scans of the spinal cord may indicate the tracts likely to be involved. It follows therefore, that there must be a more extensive lesion to explain the development of spasticity. The phenomenon of decerebrate rigidity, produced in the cat by the removal of all cortical input from the brainstem, indicates that unimpeded activity in descending projections of brainstem origin can lead to limb and axial muscle overactivity (Sherrington, 1898). It is generally believed that disruption of descending corticobulbar fibres leads to disinhibition of bulbospinal pathways (Magoun and Rhines, 1946), and that the resultant hyperreflexia is driven by unrestrained descending drives of brainstem origin (e.g., Lance, 1980; Brown, 1994), on which plastic changes in spinal circuitry may be superimposed (Burke et al., 2013). The role of descending bulbar fibres implies that there is a difference between spasticity of cortical origin and that due to cord lesions and, not surprisingly, there are differences in spinal reflex mechanisms in patients with spasticity due to cerebral and spinal lesions (Pierrot-Deseilligny and Burke, 2012). In stroke, the descending bulbar origin of ‘‘cerebral spasticity’’ posits that the changes, including the increased muscle tone, result from lesions of both the corticospinal tract and inhibitory bulbospinal pathways, the latter being the dorsal reticulospinal tract. The increase in excitability is then maintained by the facilitatory effects of the medial reticulospinal and descending vestibulospinal projections (Brown, 1994). Consistent with this, startle reflexes, mediated via excitatory reticulospinal projections, are increased in spasticity (Landis and Hunt, 1939; Jankelowitz and Colebatch, 2004a). Miller et al. controlled the level of background EMG and adjusted for the small difference between their two sides. Their findings suggest that facilitation must have occurred for the
http://dx.doi.org/10.1016/j.clinph.2014.02.023 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
2
Editorial / Clinical Neurophysiology xxx (2014) xxx–xxx
descending volley and, assuming that there has been no change in end organ sensitivity, this is consistent with a disinhibition occurring at the vestibular nucleus level. Their observations though must be taken as a surrogate measure for vestibulospinal outflow rather than being directly causative because the cVEMP is itself an inhibitory descending reflex (Colebatch and Rothwell, 2004) and the medial vestibulospinal tract does not extend below the thoracic cord (Nyberg-Hansen, 1964). Just how big a role the vestibulospinal tracts have in increasing motoneuronal excitability compared to the contribution from changes in reticulospinal outflow cannot be determined from the data reported by Miller et al. An increase in activity in the vestibulospinal tracts is accepted as part of the pathophysiology of spasticity even where abnormalities in reticulospinal outflow are considered to be the main abnormality (Brown, 1994). Miller et al. deserve credit however for providing the first clear evidence of this for human subjects. There are some uncertainties about the pathways involved in the study of Miller et al. (2014). Spasticity was measured for the elbow flexors and the ankle plantar flexors, with the measures combined into a single index. As mentioned above, the cVEMP is probably of otolith origin, mediated by vestibulocollic fibres that run in the medial vestibulospinal tract (Nyberg-Hansen, 1964). This tract terminates in the cervical region, and is therefore unlikely to be involved in driving spasticity in the lower limbs. However, in standing subjects, galvanic vestibular stimulation can produce EMG responses in lower limb muscles (tibialis anterior and soleus) and result in postural sway (Welgampola and Colebatch, 2002; Cathers et al., 2005). The responses are a mixture of opposite short-latency and medium-latency EMG bursts, presumably mediated by the lateral vestibulospinal tract and reticulospinal pathways. These responses have been attributed to different vestibular endorgans (semicircular canals and otolith organs) but, unlike startle reflexes, do not show enhancement after a corticospinal lesion (Jankelowitz and Colebatch, 2004b). A correlation of changes in the cVEMP with measures of spasticity in the limbs does not mean that the same descending pathway drives both, and it is possible that the responsible vestibular endorgans differ. Vestibulocollic projections, measured using the cVEMP, have also been investigated in focal dystonia affecting the neck but do not appear to contribute to the pathophysiology of this condition (Rosengren and Colebatch, 2010). Good research leads to the need for further enquiry, and so it is here. Further insight into the nature and extent of the disturbance of vestibular projections in spasticity may come from studies using different stimuli (e.g., bone-conducted stimuli and galvanic vestibular stimulation), from studying disturbances to postural control in patients using these stimuli, and from changes in upstream projections (e.g. the ocular VEMP).
References Brown P. Pathophysiology of spasticity. J Neurol Neurosurg Psychiatry 1994;57:773–7. Bucy PC, Keplinger JE, Siqueira EB. Destruction of the ‘‘pyramidal tract’’ in man. J Neurosurg 1964;21:385–98. Burke D. Spasticity as an adaptation to pyramidal tract injury. In: Waxman SG, editor. Advances in neurology. Functional recovery in neurological disease, vol. 47. New York: Raven Press; 1988. p. 401–423. Burke D, Wissel J, Donnan GA. Pathophysiology of spasticity in stroke. Neurology 2013;80(Suppl. 2):S20–6. Cathers I, Day BL, Fitzpatrick RC. Otolith and canal reflexes in human standing. J Physiol 2005;563:229–334. Colebatch JG, Rothwell JC. Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle. Clin Neurophysiol 2004;115:2567–73. Colebatch JG, Halmagyi GM, Skuse NF. Myogenic potentials generated by a clickevoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 1994;57:190–7. Jankelowitz SK, Colebatch JG. The acoustic startle reflex in ischemic stroke. Neurology 2004a;62:114–6. Jankelowitz SK, Colebatch JG. Galvanic evoked vestibulospinal and vestibulocollic reflexes in stroke. Clin Neurophysiol 2004b;115:1796–801. Kushiro K, Zakir M, Ogawa Y, Sato H, Uchino Y. Saccular and utricular inputs to SCM motoneurons of decerebrate cats. Exp Brain Res 1999;126:410–6. Lance JW. The control of muscle tone, reflexes, and movement: Robert Wartenberg Lecture. Neurology 1980;30:1303–13. Landis C, Hunt W, editors. The startle pattern. New York: Farrar and Rhinehart; 1939. Lawrence DG, Kuypers HGJM. The functional organization of the motor system in the monkey. I. The effects of bilateral pyramidal lesions. Brain 1968;91:1–14. Magoun HW, Rhines R. An inhibitory mechanism in the bulbar reticular formation. J Neurophysiol 1946;9:165–71. Miller DM, Klein CS, Suresh NL, Rymer WZ. Asymmetries in vestibular evoked myogenic potentials in chronic stroke survivors with spastic hypertonia: evidence for a vestibulospinal role. Clin Neurophysiol 2014 [in this issue]. Nyberg-Hansen R. Origin and termination of fibers from the vestibular nuclei descending in the medial longitudinal fasciculus. J Comp Neurol 1964;122:355–67. Pierrot-Deseilligny E, Burke D. The circuitry of the human spinal cord: spinal and corticospinal mechanisms of movement. New York: Cambridge University Press; 2012. p. 565–79 [chapter 14]. Rosengren SM, Colebatch JG. Vestibular evoked myogenic potentials are intact in cervical dystonia. Mov Disord 2010;25:2845–53. Sherrington CS. Decerebrate rigidity, and reflex coordination of movements. J Physiol 1898;22(3):19–332. Welgampola MS, Colebatch JG. Selective effects of ageing on vestibular-dependent lower limb responses following galvanic stimulation. Clin Neurophysiol 2002;113:528–34.
⇑
James G. Colebatch Department of Neurology, Prince of Wales Hospital and University of New South Wales, Sydney, NSW 2031, Australia ⇑ Tel.: +61 2 9382 2407; fax: +61 2 9382 2428. E-mail address: [email protected] David Burke Department of Neurology, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW 2006, Australia Accepted 28 February 2014 Available online xxxx
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
Vestibular function and vestibular evoked myogenic potentials (VEMPs) in spasticity See Article, pages xxx–xxx
In this issue of Clinical Neurophysiology, Miller et al. (2014) report changes in the cervical vestibular evoked myogenic potential (cVEMP) to short tone bursts in patients with spasticity. They have found that the responses are significantly larger on the side of paresis/spasticity and have shown a correlation between the degree of spasticity and the degree of asymmetry of the cVEMP. Based on these findings they propose a role for the vestibulospinal projections in causing spasticity. The findings are of potential significance in explaining the syndrome of spasticity which is commonly seen as a consequence of neurological disease affecting the corticospinal tracts. In passing it may be of interest that JGC’s original interest in the VEMP was as a means of assessing a nonpyramidal pathway (Colebatch et al., 1994). The vestibular apparatus is difficult to assess due to its size and location, and imaging has an important but limited role. Traditional methods were based upon assessing the vestibular-ocular reflex, particularly that arising from the horizontal canal, in response to rotation or thermal stimulation (caloric testing). The cVEMP represents the application of classical electrophysiological methods to the vestibular system, with the repetitive application of an effective stimulus and averaging of the result. Unlike most other evoked potentials, the cVEMP is generated by modulation of EMG activity and is not present without tonic activation of the target muscle (the sternocleidomastoid muscle; SCM). The pathway mediating the response to air conducted (AC) stimuli is now widely accepted to arise from irregularly firing afferents innervating the otoliths, mainly the saccule, synapsing in the ipsilateral vestibular nucleus and descending ipsilaterally via the medial vestibulospinal tract to synapse on the motoneurones of the SCM (Kushiro et al., 1999). Spasticity is a state of hyperreflexia, defined by a specific increase in muscle tone as well as tendon jerk reflexes in subjects at rest (Lance, 1980) and occurs only when lesions interrupt corticospinal fibres (Burke, 1988). The changes in muscle tone are best appreciated in the legs at the knee and show a characteristic velocity dependence (Lance, 1980). However, the syndrome is not a consequence of the corticospinal lesion per se (Burke, 1988). In humans limited and specific lesions cause only a restricted deficit, with increased tendon reflexes and the Babinski sign (Bucy et al., 1964) and in rhesus monkeys Lawrence and Kuypers (1968) sectioned the pyramidal tract at the decussation of the pyramids, also with limited deficits. They concluded that ‘‘in the absence of the corticospinal pathways, the descending subcorticospinal pathways
are capable of guiding a range of activity which includes independent limb movements in addition to total body–limb activity. The corticospinal pathways superimpose speed and agility upon these subcortical mechanisms, and, in addition, provide the capacity for a high degree of fractionation of movements as exemplified by individual finger movements.’’ Pathology rarely produces such selective lesions, and clinical observation, aided by improvements in imaging, suggests that a simple corticospinal lesion might result in tendon jerk hyperreflexia and the Babinski sign, but is unlikely to cause the typical changes in passive muscle tone. Changes in muscle tone in the legs in association with cervical myelopathy, for example, are usually not seen unless there are changes in the cord which probably extend beyond the corticospinal tracts. Better resolution of MRI scans of the spinal cord may indicate the tracts likely to be involved. It follows therefore, that there must be a more extensive lesion to explain the development of spasticity. The phenomenon of decerebrate rigidity, produced in the cat by the removal of all cortical input from the brainstem, indicates that unimpeded activity in descending projections of brainstem origin can lead to limb and axial muscle overactivity (Sherrington, 1898). It is generally believed that disruption of descending corticobulbar fibres leads to disinhibition of bulbospinal pathways (Magoun and Rhines, 1946), and that the resultant hyperreflexia is driven by unrestrained descending drives of brainstem origin (e.g., Lance, 1980; Brown, 1994), on which plastic changes in spinal circuitry may be superimposed (Burke et al., 2013). The role of descending bulbar fibres implies that there is a difference between spasticity of cortical origin and that due to cord lesions and, not surprisingly, there are differences in spinal reflex mechanisms in patients with spasticity due to cerebral and spinal lesions (Pierrot-Deseilligny and Burke, 2012). In stroke, the descending bulbar origin of ‘‘cerebral spasticity’’ posits that the changes, including the increased muscle tone, result from lesions of both the corticospinal tract and inhibitory bulbospinal pathways, the latter being the dorsal reticulospinal tract. The increase in excitability is then maintained by the facilitatory effects of the medial reticulospinal and descending vestibulospinal projections (Brown, 1994). Consistent with this, startle reflexes, mediated via excitatory reticulospinal projections, are increased in spasticity (Landis and Hunt, 1939; Jankelowitz and Colebatch, 2004a). Miller et al. controlled the level of background EMG and adjusted for the small difference between their two sides. Their findings suggest that facilitation must have occurred for the
http://dx.doi.org/10.1016/j.clinph.2014.02.023 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
2
Editorial / Clinical Neurophysiology xxx (2014) xxx–xxx
descending volley and, assuming that there has been no change in end organ sensitivity, this is consistent with a disinhibition occurring at the vestibular nucleus level. Their observations though must be taken as a surrogate measure for vestibulospinal outflow rather than being directly causative because the cVEMP is itself an inhibitory descending reflex (Colebatch and Rothwell, 2004) and the medial vestibulospinal tract does not extend below the thoracic cord (Nyberg-Hansen, 1964). Just how big a role the vestibulospinal tracts have in increasing motoneuronal excitability compared to the contribution from changes in reticulospinal outflow cannot be determined from the data reported by Miller et al. An increase in activity in the vestibulospinal tracts is accepted as part of the pathophysiology of spasticity even where abnormalities in reticulospinal outflow are considered to be the main abnormality (Brown, 1994). Miller et al. deserve credit however for providing the first clear evidence of this for human subjects. There are some uncertainties about the pathways involved in the study of Miller et al. (2014). Spasticity was measured for the elbow flexors and the ankle plantar flexors, with the measures combined into a single index. As mentioned above, the cVEMP is probably of otolith origin, mediated by vestibulocollic fibres that run in the medial vestibulospinal tract (Nyberg-Hansen, 1964). This tract terminates in the cervical region, and is therefore unlikely to be involved in driving spasticity in the lower limbs. However, in standing subjects, galvanic vestibular stimulation can produce EMG responses in lower limb muscles (tibialis anterior and soleus) and result in postural sway (Welgampola and Colebatch, 2002; Cathers et al., 2005). The responses are a mixture of opposite short-latency and medium-latency EMG bursts, presumably mediated by the lateral vestibulospinal tract and reticulospinal pathways. These responses have been attributed to different vestibular endorgans (semicircular canals and otolith organs) but, unlike startle reflexes, do not show enhancement after a corticospinal lesion (Jankelowitz and Colebatch, 2004b). A correlation of changes in the cVEMP with measures of spasticity in the limbs does not mean that the same descending pathway drives both, and it is possible that the responsible vestibular endorgans differ. Vestibulocollic projections, measured using the cVEMP, have also been investigated in focal dystonia affecting the neck but do not appear to contribute to the pathophysiology of this condition (Rosengren and Colebatch, 2010). Good research leads to the need for further enquiry, and so it is here. Further insight into the nature and extent of the disturbance of vestibular projections in spasticity may come from studies using different stimuli (e.g., bone-conducted stimuli and galvanic vestibular stimulation), from studying disturbances to postural control in patients using these stimuli, and from changes in upstream projections (e.g. the ocular VEMP).
References Brown P. Pathophysiology of spasticity. J Neurol Neurosurg Psychiatry 1994;57:773–7. Bucy PC, Keplinger JE, Siqueira EB. Destruction of the ‘‘pyramidal tract’’ in man. J Neurosurg 1964;21:385–98. Burke D. Spasticity as an adaptation to pyramidal tract injury. In: Waxman SG, editor. Advances in neurology. Functional recovery in neurological disease, vol. 47. New York: Raven Press; 1988. p. 401–423. Burke D, Wissel J, Donnan GA. Pathophysiology of spasticity in stroke. Neurology 2013;80(Suppl. 2):S20–6. Cathers I, Day BL, Fitzpatrick RC. Otolith and canal reflexes in human standing. J Physiol 2005;563:229–334. Colebatch JG, Rothwell JC. Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle. Clin Neurophysiol 2004;115:2567–73. Colebatch JG, Halmagyi GM, Skuse NF. Myogenic potentials generated by a clickevoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 1994;57:190–7. Jankelowitz SK, Colebatch JG. The acoustic startle reflex in ischemic stroke. Neurology 2004a;62:114–6. Jankelowitz SK, Colebatch JG. Galvanic evoked vestibulospinal and vestibulocollic reflexes in stroke. Clin Neurophysiol 2004b;115:1796–801. Kushiro K, Zakir M, Ogawa Y, Sato H, Uchino Y. Saccular and utricular inputs to SCM motoneurons of decerebrate cats. Exp Brain Res 1999;126:410–6. Lance JW. The control of muscle tone, reflexes, and movement: Robert Wartenberg Lecture. Neurology 1980;30:1303–13. Landis C, Hunt W, editors. The startle pattern. New York: Farrar and Rhinehart; 1939. Lawrence DG, Kuypers HGJM. The functional organization of the motor system in the monkey. I. The effects of bilateral pyramidal lesions. Brain 1968;91:1–14. Magoun HW, Rhines R. An inhibitory mechanism in the bulbar reticular formation. J Neurophysiol 1946;9:165–71. Miller DM, Klein CS, Suresh NL, Rymer WZ. Asymmetries in vestibular evoked myogenic potentials in chronic stroke survivors with spastic hypertonia: evidence for a vestibulospinal role. Clin Neurophysiol 2014 [in this issue]. Nyberg-Hansen R. Origin and termination of fibers from the vestibular nuclei descending in the medial longitudinal fasciculus. J Comp Neurol 1964;122:355–67. Pierrot-Deseilligny E, Burke D. The circuitry of the human spinal cord: spinal and corticospinal mechanisms of movement. New York: Cambridge University Press; 2012. p. 565–79 [chapter 14]. Rosengren SM, Colebatch JG. Vestibular evoked myogenic potentials are intact in cervical dystonia. Mov Disord 2010;25:2845–53. Sherrington CS. Decerebrate rigidity, and reflex coordination of movements. J Physiol 1898;22(3):19–332. Welgampola MS, Colebatch JG. Selective effects of ageing on vestibular-dependent lower limb responses following galvanic stimulation. Clin Neurophysiol 2002;113:528–34.
⇑
James G. Colebatch Department of Neurology, Prince of Wales Hospital and University of New South Wales, Sydney, NSW 2031, Australia ⇑ Tel.: +61 2 9382 2407; fax: +61 2 9382 2428. E-mail address: [email protected] David Burke Department of Neurology, Royal Prince Alfred Hospital and University of Sydney, Sydney, NSW 2006, Australia Accepted 28 February 2014 Available online xxxx
