Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review)
William M.Landau, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8030 ,St. Louis, MO 63110landauw@neuro.wustl.edu
Shirley Sahrmann, PhD; W. Thomas Thach, MD
Submitted February 11, 2009
Advocacy of botulinum for spasticity fails claimed “evidence-based” standards: unconflicted, objective measures, blinded controls, independent replication. [1] Unlike symptomatic headache, spasticity has a scientific definition: “motor disorder characterized by velocity–dependent increase in tonic stretch reflexes (‘muscle tone’) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex as one component of the upper motor neuron syndrome [UMNS, all morbid effects of forebrain disconnection from spinal cord/brainstem]. … negative symptoms [are] the pattern of weakness and loss of dexterity caused by withdrawal of the influence of these descending motor pathways.” [3]
Thus, spasticity is only the product of professional examination, neither cause nor synonym of UMNS, and not consistently correlated with severity of motor performance disability. [4-7, e1-e3] Deficient deftness and force result directly from impaired control of recruitment and firing frequency of motoneurons that comprise the final common path for a specific task. [e4-e16] Most weakness is neither attributable to mistaken reflex opposition [e17] nor myopathic failure. [e18] At rest spastic muscle is flaccid and electromyographically silent. [e4] Even the chronic decerebrate state has passive limb postures with brisk tendon jerks. [e19-e22]
The assessors state “Resistance to passive movement has not been shown to correlate with active function,” but accept the subjective non- parametric Ashworth spasticity scale, “global satisfaction scores,” and “passive function” by “subjects, family members, or clinicians”: truly placebo by acclamation. Subjective labels for clumsiness like “stiffness/ tightness” are not evidence for curable reflex mechanism. Their advertisement “for patients and families” that botulinum injections “block nerve signals that cause muscle spasms or pain” is deceptively misleading. The only certain effect is weakness of injected muscle for all activities, voluntary, involuntary, and reflex. No evidence supports their presumptive speculation that paralytic injection may improve muscle weakness, soft tissue contracture, and muscle overactivity by reducing spastic co-contraction, decreasing spastic dystonia, easing muscle stretch, and increasing antagonistic torque. Measurements for comfort/nursing care by paralysis of certain muscles were not ascertained. Substantive performance gain in adults is yet to be proved.
Cerebral palsy impairs projections from corticospinal neurons, basal ganglia, and often cerebellum/brainstem. [e-16] Deficits of gait, limb growth, dexterity, and speech are not simply juvenile spasticity. Whether prescription botulinum beyond research protocols improves operative morbidity and permanent functional outcome also remains still to be seen. [e23]
The false premise that reflex spasticity contributes materially to negative symptoms is unnecessary. Objective measures of botulinum efficacy for any UMNS impairment merit Cochrane collaboration standard evaluation.
References
3. Lance JW. Symposium Synopsis. In: Feldman RG, Young RR, Koella WP, ed. Spasticity: Disordered Motor Control. Chicago: Year Book, 1980:485.
4. Twitchell TE. The restoration of motor function following hemiplegia in man. Brain 1951;74;443-480.
5. Landau WM, Weaver RA, Hornbein TF. Fusimotor nerve function in man: Differential nerve block studies in normal subjects and in spasticity and rigidity. Arch Neurol 1961:3:10-23.
6. Landau WM. Clinical Neuromythology II. Parables of palsy pills and PT pedagogy: a spastic dialectic. Neurology 1988;38:1496-1499.
7. Landau WM, Hunt CC. Dorsal rhizotomy, a treatment of unproven efficacy. J Child Neurol 1990;5:174-178.
[ REFERENCES e1-e23 will be considered as DATA SUPPLEMENT electronic REFERENCE material]
*****
e2. Sommerfeld DK, Eek EU, Svensson AK, et al. Spasticity after stroke: its occurrence and association with motor impairments and activity limitations. Stroke 2004;35:134-139.
e3. Landau WM. Letter to the Editor: Spasticity after stroke, Why bother? Stroke 2004; 35:1787-1788.
e4. Hoefer PF, Putnam TJ. Action potentials of muscles in “spastic” conditions. Arch Neurol Psychiatr 1940;43:1-22.
e5. McComas AJ, Sica, REP, Upton ARM, et al. Functional changes in motoneurons of hemiparetic patients. J Neurol Neurosurg Psychiat 1973;36:183-193.
e6. Young RR, Shahani BT. A clinical neurophysiological analysis of single motor unit discharge patterns in spasticity. In: Feldman RG, Young RR, Koella WP, ed. Spasticity: Disordered Motor Control. Chicago: Year Book, 1980:219-231.
e7. Petajan JH. Motor unit control in spasticity. In: Feldman RG, Young RR, Koella WP, ed. Spasticity: Disordered Motor Control. Chicago: Year Book, 1980:233-247.
e8. Grimby L, Hannerz J, Rånlund T. Disturbances in the voluntary recruitment order of anterior tibial motor units in spastic paraparesis upon fatigue. J Neurol Neurosurg Psychiat 1974;37:40-46.
e9. Rosenfalck A, Andreassen S. Impaired regulation of force and firing pattern of single motor units in patients with spasticity. J Neurol Neurosurg Psychiat 1980;43:907-916.
e10. Tang A, Rymer WZ. Abnormal force-EMG relations in paretic limbs of hemiparetic human subjects. J Neurol Neurosurg Psychiat 1981;44:690- 698.
e11. Fitts SS, Hammond MC, Kraft GH, et al. Quantification of gaps in the EMG interference pattern in chronic hemiparesis. Electroenceph Clin Neurophysiol 1989; 73:225-232.
e12. Gemperline JJ, Allen S, Walk D, et al. Characteristics of motor unit discharge in subjects with hemiparesis. Muscle Nerve 1995;18:1101- 1114.
e13. Frontera WR, Grimby L, Larsson L. Firing rate of the lower motoneuron and contractile properties of its muscle fibers after upper motoneuron lesion in man. Muscle Nerve 1997;20:938-947.
e14. Frascarelli M, Mastrogregori L, Conforti L. Initial motor unit recruitment in patients with spastic hemiplegia. Electromyogr Clin Neurophysiol 1998;38:267-271.
e15. Canning CG, Ada L, O’Dwyer NJ. Abnormal muscle activation characteristics associated with loss of dexterity after stroke. 2000; J Neurol Sci 2000;176:45-56.
e16. Rose J, McGill KC. Neuromuscular activation and motor-unit firing characteristics in cerebral palsy. Dev Med Child Neurol 2005;47:329-336.
e17. Sahrmann SA, Norton BJ. The relationship of voluntary movement to spasticity in the upper motor neuron syndrome. Ann Neurol 1977;2:460-465.
e18. Landau WM and Sahrmann SA. Preservation of directly stimulated muscle strength in hemiplegia due to stroke. Arch Neurol 2002;59:1453- 1457.
e19. Feldman MH. The decerebrate state in the primate. I. Studies in Monkeys. Arch Neurol 1971;25:501-516.
e20. Feldman MH, Sahrmann S. The decerebrate state in the primate. II. Studies in Man. Arch Neurol 1971;25:517-525.
e21. Feldman MH. Physiological observations in a chronic case of “locked-in” syndrome. 1971;21:460-478.
e22. Bazett HC, Penfield WG. A study of the Sherrington decerebrate animal in the chronic as well as the acute condition. Brain 1922;45:185- 265.
e23. Moore AP, Ade-Hall RA, Tudor Smith C, et al. Two-year placebo- controlled trial of botulinum toxin A for leg spasticity in cerebral palsy. Neurology 2008;71:122-128.
Advocacy of botulinum for spasticity fails claimed “evidence-based” standards: unconflicted, objective measures, blinded controls, independent replication. [1] Unlike symptomatic headache, spasticity has a scientific definition: “motor disorder characterized by velocity–dependent increase in tonic stretch reflexes (‘muscle tone’) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex as one component of the upper motor neuron syndrome [UMNS, all morbid effects of forebrain disconnection from spinal cord/brainstem]. … negative symptoms [are] the pattern of weakness and loss of dexterity caused by withdrawal of the influence of these descending motor pathways.” [3]
Thus, spasticity is only the product of professional examination, neither cause nor synonym of UMNS, and not consistently correlated with severity of motor performance disability. [4-7, e1-e3] Deficient deftness and force result directly from impaired control of recruitment and firing frequency of motoneurons that comprise the final common path for a specific task. [e4-e16] Most weakness is neither attributable to mistaken reflex opposition [e17] nor myopathic failure. [e18] At rest spastic muscle is flaccid and electromyographically silent. [e4] Even the chronic decerebrate state has passive limb postures with brisk tendon jerks. [e19-e22]
The assessors state “Resistance to passive movement has not been shown to correlate with active function,” but accept the subjective non- parametric Ashworth spasticity scale, “global satisfaction scores,” and “passive function” by “subjects, family members, or clinicians”: truly placebo by acclamation. Subjective labels for clumsiness like “stiffness/ tightness” are not evidence for curable reflex mechanism. Their advertisement “for patients and families” that botulinum injections “block nerve signals that cause muscle spasms or pain” is deceptively misleading. The only certain effect is weakness of injected muscle for all activities, voluntary, involuntary, and reflex. No evidence supports their presumptive speculation that paralytic injection may improve muscle weakness, soft tissue contracture, and muscle overactivity by reducing spastic co-contraction, decreasing spastic dystonia, easing muscle stretch, and increasing antagonistic torque. Measurements for comfort/nursing care by paralysis of certain muscles were not ascertained. Substantive performance gain in adults is yet to be proved.
Cerebral palsy impairs projections from corticospinal neurons, basal ganglia, and often cerebellum/brainstem. [e-16] Deficits of gait, limb growth, dexterity, and speech are not simply juvenile spasticity. Whether prescription botulinum beyond research protocols improves operative morbidity and permanent functional outcome also remains still to be seen. [e23]
The false premise that reflex spasticity contributes materially to negative symptoms is unnecessary. Objective measures of botulinum efficacy for any UMNS impairment merit Cochrane collaboration standard evaluation.
References
3. Lance JW. Symposium Synopsis. In: Feldman RG, Young RR, Koella WP, ed. Spasticity: Disordered Motor Control. Chicago: Year Book, 1980:485.
4. Twitchell TE. The restoration of motor function following hemiplegia in man. Brain 1951;74;443-480.
5. Landau WM, Weaver RA, Hornbein TF. Fusimotor nerve function in man: Differential nerve block studies in normal subjects and in spasticity and rigidity. Arch Neurol 1961:3:10-23.
6. Landau WM. Clinical Neuromythology II. Parables of palsy pills and PT pedagogy: a spastic dialectic. Neurology 1988;38:1496-1499.
7. Landau WM, Hunt CC. Dorsal rhizotomy, a treatment of unproven efficacy. J Child Neurol 1990;5:174-178.
[ REFERENCES e1-e23 will be considered as DATA SUPPLEMENT electronic REFERENCE material] *****
e1. Landau WM. Muscle tone: hypertonus, spasticity, rigidity. In: Elsevier’s Encyclopedia of Neuroscience, 3rd Edition 2001;1-5.
e2. Sommerfeld DK, Eek EU, Svensson AK, et al. Spasticity after stroke: its occurrence and association with motor impairments and activity limitations. Stroke 2004;35:134-139.
e3. Landau WM. Letter to the Editor: Spasticity after stroke, Why bother? Stroke 2004; 35:1787-1788.
e4. Hoefer PF, Putnam TJ. Action potentials of muscles in “spastic” conditions. Arch Neurol Psychiatr 1940;43:1-22.
e5. McComas AJ, Sica, REP, Upton ARM, et al. Functional changes in motoneurons of hemiparetic patients. J Neurol Neurosurg Psychiat 1973;36:183-193.
e6. Young RR, Shahani BT. A clinical neurophysiological analysis of single motor unit discharge patterns in spasticity. In: Feldman RG, Young RR, Koella WP, ed. Spasticity: Disordered Motor Control. Chicago: Year Book, 1980:219-231.
e7. Petajan JH. Motor unit control in spasticity. In: Feldman RG, Young RR, Koella WP, ed. Spasticity: Disordered Motor Control. Chicago: Year Book, 1980:233-247.
e8. Grimby L, Hannerz J, Rånlund T. Disturbances in the voluntary recruitment order of anterior tibial motor units in spastic paraparesis upon fatigue. J Neurol Neurosurg Psychiat 1974;37:40-46.
e9. Rosenfalck A, Andreassen S. Impaired regulation of force and firing pattern of single motor units in patients with spasticity. J Neurol Neurosurg Psychiat 1980;43:907-916.
e10. Tang A, Rymer WZ. Abnormal force-EMG relations in paretic limbs of hemiparetic human subjects. J Neurol Neurosurg Psychiat 1981;44:690- 698.
e11. Fitts SS, Hammond MC, Kraft GH, et al. Quantification of gaps in the EMG interference pattern in chronic hemiparesis. Electroenceph Clin Neurophysiol 1989; 73:225-232.
e12. Gemperline JJ, Allen S, Walk D, et al. Characteristics of motor unit discharge in subjects with hemiparesis. Muscle Nerve 1995;18:1101- 1114.
e13. Frontera WR, Grimby L, Larsson L. Firing rate of the lower motoneuron and contractile properties of its muscle fibers after upper motoneuron lesion in man. Muscle Nerve 1997;20:938-947.
e14. Frascarelli M, Mastrogregori L, Conforti L. Initial motor unit recruitment in patients with spastic hemiplegia. Electromyogr Clin Neurophysiol 1998;38:267-271.
e15. Canning CG, Ada L, O’Dwyer NJ. Abnormal muscle activation characteristics associated with loss of dexterity after stroke. 2000; J Neurol Sci 2000;176:45-56.
e16. Rose J, McGill KC. Neuromuscular activation and motor-unit firing characteristics in cerebral palsy. Dev Med Child Neurol 2005;47:329-336.
e17. Sahrmann SA, Norton BJ. The relationship of voluntary movement to spasticity in the upper motor neuron syndrome. Ann Neurol 1977;2:460-465.
e18. Landau WM and Sahrmann SA. Preservation of directly stimulated muscle strength in hemiplegia due to stroke. Arch Neurol 2002;59:1453- 1457.
e19. Feldman MH. The decerebrate state in the primate. I. Studies in Monkeys. Arch Neurol 1971;25:501-516.
e20. Feldman MH, Sahrmann S. The decerebrate state in the primate. II. Studies in Man. Arch Neurol 1971;25:517-525.
e21. Feldman MH. Physiological observations in a chronic case of “locked-in” syndrome. 1971;21:460-478.
e22. Bazett HC, Penfield WG. A study of the Sherrington decerebrate animal in the chronic as well as the acute condition. Brain 1922;45:185- 265.
e23. Moore AP, Ade-Hall RA, Tudor Smith C, et al. Two-year placebo- controlled trial of botulinum toxin A for leg spasticity in cerebral palsy. Neurology 2008;71:122-128.
Disclosure: The authors report no disclosures.