Posts Tagged biological infrastructure

[Abstract + References] New Treatment Approaches on the Horizon for Spastic Hemiparesis – PM&R


This article presents 2 recent articles that propose novel interventions for treating spastic hemiparesis by changing biological infrastructure. In 18 patients with unilateral spastic arm paralysis due to chronic cerebral injury greater than 5 years’ duration, Zheng et al transferred the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed. Over a follow-up period of 12 months, they found greater improvement in function and a reduction of spasticity compared to rehabilitation alone. Using functional magnetic resonance imaging, they also found evidence for physiological connectivity between the ipsilateral cerebral hemisphere and the paralyzed hand. In the second article, Raghavan et al examine the concept of stiffness, a common symptom in patients with spastic hemiparesis, as a physical change in the infrastructure of muscle. Raghavan’s non-neural hyaluronan hypothesis postulates that an accumulation of hyaluronan within spastic muscles promotes the development of muscle stiffness in patients with an upper motor neuron syndrome (UMNS). In a case series of 20 patients with spastic hemiparesis, Raghavan et al report that upper limb intramuscular injections of hyaluronidase increased passive and active joint movement and reduced muscle stiffness. Interventions that change biological infrastructure in UMNS is a paradigm on the horizon that bears watching.


  1. Zheng, M.X., Hua, X.Y., Feng, J.T. et al, Trial of contralateral seventh cervical nerve transfer for spastic arm paralysis. N Engl J Med2018;378:22–34.
  2. Feigin, V.L., Krishnamurthi, R.V., Parmar, P. et al, Update on the global burden of ischemic and hemorrhagic stroke in 1990–2013: The GBD 2013 study. Neuroepidemiology2015;45:161–176.
  3. Langhorne, P., Coupar, F., Pollock, A. Motor recovery after stroke: A systematic review. Lancet Neurol2009;8:741–754.
  4. Grefkes, C., Ward, N.S. Cortical reorganization after stroke: How much and how functional?.Neuroscientist2014;20:56–70.
  5. Seidler, R.D., Noll, D.C., Thiers, G. Feedforward and feedback processes in motor control.Neuroimage2004;22:1775–1783.
  6. Verstynen, T., Diedrichsen, J., Albert, N., Aparicio, P., Ivry, R.B. Ipsilateral motor cortex activity during unimanual hand movements relates to task complexity. J Neurophysiol2005;93:1209–1222.
  7. Lotze, M., Markert, J., Sauseng, P., Hoppe, J., Plewnia, C., Gerloff, C. The role of multiple contralesional motor areas for complex hand movements after internal capsular lesion. J Neurosci2006;26:6096–6102.
  8. Buetefisch, C.M. Role of the contralesional hemisphere in post-stroke recovery of upper extremity motor function. Front Neurol2015;6:214.
  9. Ziemann, U., Ishii, K., Borgheresi, A. et al, Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles. J Physiol1999;518:895–906.
  10. Jankowska, E., Edgley, S.A. How can corticospinal tract neurons contribute to ipsilateral movements? A question with implications for recovery of motor functions. Neuroscientist2006;12:67–79.
  11. Currà, A., Trompetto, C., Abbruzzese, G., Berardelli, A. Central effects of botulinum toxin type A: Evidence and supposition. Mov Disord2004;19:S60–S64.
  12. Caleo, M., Antonucci, F., Restani, L., Mazzocchio, R. A reappraisal of the central effects of botulinum neurotoxin type A: By what mechanism?. J Neurochem2009;109:15–24.
  13. Palomar, F.J., Mir, P. Neurophysiological changes after intramuscular injection of botulinum toxin.Clin Neurophysiol2012;123:54–60.
  14. Spinner, R.J., Shin, A.Y., Bishop, A.T. Rewiring to regain function in patients with spastic hemiplegia. N Engl J Med2018;378:83–84.
  15. Raghavan, P., Lub, Y., Mirchandani, M., Stecco, A. Human recombinant hyaluronidase injections for upper limb muscle stiffness in individuals with cerebral injury: A case series. EBioMedicine2016;9:306–313.
  16. Lance, J.W. The control of muscle tone, reflexes, and movement: Robert Wartenberg lecture.Neurology1980;30:1303–1313.
  17. Stecco, A., Stecco, C., Raghavan, P. Peripheral mechanisms of spasticity and treatment implications. Curr Phys Med Rehabil Rep2014;2:121–127.
  18. Piehl-Aulin, K., Laurent, C., Engström-Laurent, A., Hellström, S., Henriksson, J. Hyaluronan in human skeletal muscle of lower extremity: Concentration, distribution and effect of exercise. J Appl Physiol (1985)1991;71:2493–2498.
  19. Springer, J., Schust, S., Peske, K. et al, Catabolic signaling and muscle wasting after acute ischemic stroke in mice: Indication for a stroke-specific sarcopenia. Stroke2014;45:3675–3683.
  20. de Bruin, M., Smeulders, M.J., Kreulen, M., Huijing, P.A., Jaspers, R.T. Intramuscular connective tissue differences in spastic and control muscle: A mechanical and histological study. PLoS One2014;9:e101038.
  21. Al’Qteishat, A., Gaffney, J., Krupinski, J. et al, Changes in hyaluronan production and metabolism following ischaemic stroke in man. Brain2006;129:2158–2176.
  22. Okita, M., Yoshimura, T., Nakano, J., Motomura, M., Eguchi, K. Effects of reduced joint mobility on sarcomere length, collagen fibril arrangement in the endomysium and hyaluronan in rat soleus muscle. J Muscle Res Cell Motil2004;25:159–166.
  23. Matteini, P., Dei, L., Carretti, E., Volpi, N., Goti, A., Pini, R. Structural behavior of highly concentrated hyaluronan. Biomacromolecules2009;10:1516–1522.
  24. Cowman, M.K., Schmidt, T.A., Raghavan, P., Stecco, A. Viscoelastic properties of hyaluronan in physiological conditions. F1000Res2015;4:622.
  25. Purslow, P.P. Muscle fascia and force transmission. J Bodyw Mov Ther2010;14:411–417.
  26. Stecco, C. The Functional Atlas of the Human Fascial System. Churchill LivingstoneLondon2015.
  27. Jenkins, R.H., Thomas, G.J., Williams, J.D., Steadman, R. Myofibroblastic differentiation leads to hyaluronan accumulation through reduced hyaluronan turnover. J Biol Chem2004;279:41453–41460.
  28. Fleuren, J.F., Voerman, G.E., Erren-Wolters, C.V. et al, Stop using the Ashworth Scale for the assessment of spasticity. J Neurol Neurosurg Psychiatry2010;81:46–52.
  29. Phadke, C.P., Balasubramanian, C.K., Holz, A., Davidson, C., Ismail, F., Boulias, C. Adverse clinical effects of botulinum toxin intramuscular injections for spasticity. Can J Neurol Sci2016;43:298–310.

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