Vorträge und Posterpräsentationen (mit Tagungsband-Eintrag):
K. Minassian, U Hofstötter, S. M. Danner, B. Freundl, H. Binder, W. Mayr, F. Rattay, M. Dimitrijevic:
"Neurophysiology of the human lumbar spinal rhythm and pattern generation under sustained, repetitive stimulation";
Vortrag: International Symposium on Spasticity and Neural Control of Movement with the 30th Dr. Janez Faganel Memorial Lecture,
Ljubljana, Slovenia (eingeladen);
04.09.2014
- 06.09.2014; in: "International Symposium on Spasticity and Neural Control of Movement with the 30th Dr. Janez Faganel Memorial Lecture: Program and Proceedings",
J. Zidar (Hrg.);
Section for Clinical Neurophysiology of the Slovenian Medical Association,
Ljubljana, Slovenia
(2014),
ISBN: 978-961-6956-04-8;
S. 57
- 59.
Kurzfassung englisch:
Epidural spinal cord stimulation (SCS) became available in 1967 when neurosurgeon Norman
Shealy implanted the first neuromodulative device for the relief of intractable pain (1). The
application of SCS in motor disorders resulted from observations made when treating a
multiple sclerosis patient for pain (2, 3). SCS controlled the pain and, in addition, improved
voluntary motor function. The treatment of a large number of patients with various motor
disorders followed, and the beneficial responses included improved bladder function, reduced
spasticity, as well as a feeling of lightness of the legs and decreased fatigue, the ability to
stand and walk more easily, increased endurance, and partial regain of lost motor function
(4, 5). In spinal cord injured (SCI) individuals, the alleviation of severe spasticity by SCS was
repetitively demonstrated (6-8). In a motor-incomplete SCI person who underwent SCS for
the management of severe intractable spasms, Barolat et al. (1986) were among the first to
report on regained volitional control over some movements of otherwise paralyzed lower
limb muscles that was present only under epidural SCS (9). Recent reports of apparently
motor complete SCI individuals, who regained some supraspinal control over paralyzed legs
during epidural stimulation (10, 11), generated again great interest in SCS for the augmentation
of residual function after severe SCI injury.
Electrophysiological studies of the effects of SCS indicated that the stimulation could act at
brainstem as well as spinal cord levels (12, 13). The generation of rhythmic leg muscle
activity by lumbar SCS at 25-50 Hz in individuals with cervical or thoracic motor-complete
SCI particularly revealed the activation of lumbar pattern generating circuitry (14). Here, we
will summarize some of our studies that aimed at understanding the mechanisms underlying
the operation of this spinal circuitry.
We found that in motor-complete SCI individuals, the SCS-elicited motor outputs are comprised
of series of posterior root-muscle (PRM) reflexes, i.e., large-afferent-induced spinal
reflex responses initiated in the posterior roots and recorded by surface-EMG from many
lower-limb muscles bilaterally (15). Burst-like activities consisted of modulated PRM reflexes
with waxing and waning amplitudes. The latencies of the PRM reflexes that constituted
these burst-like motor outputs demonstrated phase-dependent modifications. Bursts
generated during extension-like phases consisted of short-latency, presumably monosynaptic
PRM reflexes. Within the bursts of flexion-like phases, these short-latency PRM reflexes
could be completely supressed and replaced by a delayed-latency PRM reflex (delayed by
approx. 8 ms). We have suggested that the repetitive stimulation generates motor output
trans-synaptically through more direct pathways, evoking PRM reflexes, and recruits spinal
interneuronal circuits as well that subsequently modulate the concomitantly elicited PRM
reflex output (16, 17).
To reveal the functional organization of the spinal circuits that rhythmically modulated the
PRM reflexes, we studied a variety of rhythmic EMG patterns generated by the functionally
isolated human lumbar spinal cord in response to SCS, and investigated basic temporal
components shared across these patterns (18). A statistical decomposition technique applied
to the EMG data across subjects, muscles and samples of rhythmic patterns identified
three common temporal components, basic or shared activation patterns, underlying the
profiles of muscle activity. Two of these basic patterns controlled muscles to contract either
synchronously or alternatingly during extension- and flexion-like phases. The third basic
pattern contributed to the observed muscle activities independently from these extensorand
flexor-related basic patterns. Burst generators that impose specific spatiotemporally
organised activation on the lumbosacral motoneuron pools could have implemented these
basic patterns.
In conclusion, we have shown that even after severe cervical or thoracic SCI, the human
lumbosacral neural circuits can continue to generate rhythmic motor output to paralyzed leg
muscles in response to sustained, repetitive posterior-root stimulation. The motor output is
generated through the stimulation of more direct afferent projections to the motoneuron
pools, as well as the activation of interneuronal circuits of the spinal cord. Specifically, it
results from the rhythmic modulation of monosynaptic spinal reflex circuits as well as from
the selection of alternative oligo-synaptic spinal pathways during flexion-like phases. The
functional organization of the lumbosacral interneuronal network that rhythmically modulated
the motor output may rely on burst-generating elements that flexibly combine to obtain a
wide range of locomotor outputs.
References
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3. Cook AW. Electrical stimulation in multiple sclerosis. Hosp Pract 1976; 11: 51-8.
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12. Sedgwick EM, Illis LS, Tallis RC, Thornton AR, Abraham P, El-Negamy E, et al. Evoked potentials and contingent negative variation during treatment of multiple sclerosis with spinal cord stimulation. J Neurol Neurosurg Psychiatry 1980; 43: 15-24.
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14. Dimitrijevic MR, Gerasimenko Y, Pinter MM. Evidence for a spinal central pattern generator in humans. Ann N Y Acad Sci 1998; 860: 360-76.
15. Minassian K, Jilge B, Rattay F, Pinter MM, Binder H, Gerstenbrand F, 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. Spinal Cord 2004; 42: 401-16.
16. Minassian K, Persy I, Rattay F, Pinter MM, Kern H, Dimitrijevic MR. Human lumbar cord circuitries can be activated by extrinsic tonic input to generate locomotor-like activity. Hum Mov Sci 2007; 26: 275-95.
17. Capogrosso M, Wenger N, Raspopovic S, Musienko P, Beauparlant J, Bassi Luciani L, et al. A computational model for epidural electrical stimulation of spinal sensorimotor circuits. J Neurosci 2013;
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18. Danner SM, Rattay F, Hofstoetter US, Dimitrijevic MR, Minassian K. Locomotor rhythm and pattern generating networks of the human lumbar spinal cord: an electrophysiological and computer modeling study. BMC Neuroscience 2013; 14 (Suppl 1): P274.
Zugeordnete Projekte:
Projektleitung Frank Rattay:
Life Sciences - Linking Research and Patients' Needs Augmentation of residual neural control by non-invasive spinal cord stimulation to modify spasticity in spinal cord injured people
Erstellt aus der Publikationsdatenbank der Technischen Universität Wien.