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Furosemide unmasks inhibitory dysfunction following spinal cord injury in humans: Implication for spasticity
e234
Posters (First Part) / Annals of Physical and Rehabilitation Medicine 61S (2018) e103–e308
ISPR8-0794
ISPR8-0889
Furosemide unmasks inhibitory dysfunction following spinal cord injury in humans: Implication for spasticity
Spinal cord injury trends in the United States, 1972–2017
A. Lackmy-Vallee 1 , W. Klomjai 2 , N. Roche 3 , J.C. Lamy 1 , B. Bussel 4 , D. Bensmail 4 , P. Pradat-Diehl 5 , R. Katz 1,∗ 1 Sorbonne Universite, laboratoire d’imagerie médicale, Paris, France 2 Mahidol University, Faculty of physical therapy, Nakonpathom, Thailand 3 Université Versailles-Saint-Quentin, équipe associée 4497, Garches, France 4 AP–HP, hopital Raymond-Poincaré, service de médecine physique et réadaptation, Garches, France 5 AP–HP, Hopitaux universitaires Pitié-Salpétrière, Charles Foix, Service de médecine Physique et Réadaptation, Paris, France ∗ Corresponding author. E-mail address: [email protected] (A. Lackmy-Vallee), [email protected] (R. Katz) Introduction/Background Potassium chloride co-transporter KCC2 plays a key role in chloride homeostasis and inhibitory functions in mature neurons. Animal studies have demonstrated a down-regulation of KCC2 function following spinal cord transection. This reverses the inhibitory effect of gamma aminobutyric acid and glycine to an excitatory effect, resulting in reduced inhibition. We have previously demonstrated in healthy subjects that furosemide, a potent KCC2 antagonist, can be readily used to assess inhibitory synapse efficiency in humans. We have shown that furosemide reduces both presynaptic and postsynaptic inhibitions without altering monosynaptic excitatory transmission [1] thus suggesting that furosemide can be used as a probe to study the function of inhibitory synapses in humans. The aim of this presentation is to explore if in paraplegic patients a down regulation of KCC2 may contribute to the reflex hyperexcitability following spinal cord injury. Material and method In the present study, we used a similar experimental design to that developed in healthy subjects: the study of the effects of 40 mg of furosemide intake per os onto soleus H reflexes conditioned by inhibitory percutaneous stimulations were explored during 60 minutes following furosemide intake. Results Furosemide fails to modulate both pre- and postsynaptic inhibitions relayed to soleus spinal motoneurons in spinal cord injured patients. The reduced inhibitory effect of furosemide in spinal cord injury patients suggests a KCC2 dysfunction in human spinal neurons, resulting in a regression to immature inhibitory synapses, similarly to animal models. Conclusion The reversal from inhibitory to excitatory synapses may be an important contributor to hyperreflexia in spinal cord injury and may lead to novel therapeutic strategies centred on chloride homeostasis. Keywords Spinal cord injury; Spasticity; Neurophysiology Disclosure of interest The authors declare that they have no competing interest. Reference [1] Klomjai W, et al. J Physiol 2014;592:2865–79. https://doi.org/10.1016/j.rehab.2018.05.541
Y. Chen ∗ , H. Wen , M. DeVivo University of Alabama at Birmingham, Physical Medicine and Rehabilitation, Birmingham, USA ∗ Corresponding author. E-mail address: [email protected] (Y. Chen) Introduction/Background This cross-sectional analysis of longitudinal data was conducted to document demographic and clinical characteristics of newly injured and prevalent population with spinal cord injury (SCI) in the United States. Material and method 32.727 people with traumatic SCI who received initial hospital care from one of the 30 SCI Model Systems Centers since the early 1970s were included in the analyses with data on demographic, injury and medical characteristics, and psychosocial wellbeing obtained during the initial hospitalization and at year 1, 5, and every 5 years after injury through 2017. Results Age at injury has increased from 29 years in the 1970s to 42 years currently. This aging phenomenon was noted for all sexes, races, and etiologies except acts of violence. Although vehicular crashes continue to be the leading cause of SCI overall, injuries due to falls have increased over time particularly among those aged 46 years and older. Injuries resulting in tetraplegia are increasing while neurologically complete injuries are decreasing. Lengths of stay in the acute hospital and rehabilitation unit have declined. About 30% of persons with SCI are re-hospitalized during any given year following injury. Diseases of the genitourinary system are the leading cause of re-hospitalization. Mortality rates are significantly higher during the first year after injury. The life expectancy has improved but remain significantly below life expectancies of persons without SCI. The causes of death that have the greatest impact on reduced life expectancy over the last 5 decades are pneumonia and septicemia. Conclusion Study findings call for geriatrics expertise in the care for SCI and also highlights the need for a multi-dimensional risk assessment and intervention to reduce falls and SCI in older adults. Within the prevalent population, those who survive many years typically will have less severe injuries, high levels of independence and overall good health. Keywords Spinal cord injury; Epidemiology; Trends Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.rehab.2018.05.542 ISPR8-1700
Clinical efficacy of upper limb robotic therapy in cervical spinal cord injured patients: A randomized control trial Z.A. Han 1,∗ , J. Kim 2 , H.J. Lee 1 , H.R. Kim 1 , D.Y. Cho 3 , B.S. Lee 1 , J. Kim 1 , J.E. Lim 3 , H.Y. Kim 3 1 National rehabilitation center, spinal cord injury rehabilitation, Seoul, Republic of Korea 2 National rehabilitation center, rehabilitation, Seoul, Republic of Korea 3 National rehabilitation center, Assistive technology, Seoul, Republic of Korea ∗ Corresponding author. E-mail address: [email protected] (Z.A. Han) Introduction/Background The efficacy of upper limb robotic therapy (UERs) in cervical SCI patients is relatively limited. With a better understanding of the effect of UER in cervical SCI patients, development of therapy programs with more adequate dosing, method, and safe protocols along with valid assessment tools will be possible in the future. This study evaluates the potential
Posters (First Part) / Annals of Physical and Rehabilitation Medicine 61S (2018) e103–e308
ISPR8-0794
ISPR8-0889
Furosemide unmasks inhibitory dysfunction following spinal cord injury in humans: Implication for spasticity
Spinal cord injury trends in the United States, 1972–2017
A. Lackmy-Vallee 1 , W. Klomjai 2 , N. Roche 3 , J.C. Lamy 1 , B. Bussel 4 , D. Bensmail 4 , P. Pradat-Diehl 5 , R. Katz 1,∗ 1 Sorbonne Universite, laboratoire d’imagerie médicale, Paris, France 2 Mahidol University, Faculty of physical therapy, Nakonpathom, Thailand 3 Université Versailles-Saint-Quentin, équipe associée 4497, Garches, France 4 AP–HP, hopital Raymond-Poincaré, service de médecine physique et réadaptation, Garches, France 5 AP–HP, Hopitaux universitaires Pitié-Salpétrière, Charles Foix, Service de médecine Physique et Réadaptation, Paris, France ∗ Corresponding author. E-mail address: [email protected] (A. Lackmy-Vallee), [email protected] (R. Katz) Introduction/Background Potassium chloride co-transporter KCC2 plays a key role in chloride homeostasis and inhibitory functions in mature neurons. Animal studies have demonstrated a down-regulation of KCC2 function following spinal cord transection. This reverses the inhibitory effect of gamma aminobutyric acid and glycine to an excitatory effect, resulting in reduced inhibition. We have previously demonstrated in healthy subjects that furosemide, a potent KCC2 antagonist, can be readily used to assess inhibitory synapse efficiency in humans. We have shown that furosemide reduces both presynaptic and postsynaptic inhibitions without altering monosynaptic excitatory transmission [1] thus suggesting that furosemide can be used as a probe to study the function of inhibitory synapses in humans. The aim of this presentation is to explore if in paraplegic patients a down regulation of KCC2 may contribute to the reflex hyperexcitability following spinal cord injury. Material and method In the present study, we used a similar experimental design to that developed in healthy subjects: the study of the effects of 40 mg of furosemide intake per os onto soleus H reflexes conditioned by inhibitory percutaneous stimulations were explored during 60 minutes following furosemide intake. Results Furosemide fails to modulate both pre- and postsynaptic inhibitions relayed to soleus spinal motoneurons in spinal cord injured patients. The reduced inhibitory effect of furosemide in spinal cord injury patients suggests a KCC2 dysfunction in human spinal neurons, resulting in a regression to immature inhibitory synapses, similarly to animal models. Conclusion The reversal from inhibitory to excitatory synapses may be an important contributor to hyperreflexia in spinal cord injury and may lead to novel therapeutic strategies centred on chloride homeostasis. Keywords Spinal cord injury; Spasticity; Neurophysiology Disclosure of interest The authors declare that they have no competing interest. Reference [1] Klomjai W, et al. J Physiol 2014;592:2865–79. https://doi.org/10.1016/j.rehab.2018.05.541
Y. Chen ∗ , H. Wen , M. DeVivo University of Alabama at Birmingham, Physical Medicine and Rehabilitation, Birmingham, USA ∗ Corresponding author. E-mail address: [email protected] (Y. Chen) Introduction/Background This cross-sectional analysis of longitudinal data was conducted to document demographic and clinical characteristics of newly injured and prevalent population with spinal cord injury (SCI) in the United States. Material and method 32.727 people with traumatic SCI who received initial hospital care from one of the 30 SCI Model Systems Centers since the early 1970s were included in the analyses with data on demographic, injury and medical characteristics, and psychosocial wellbeing obtained during the initial hospitalization and at year 1, 5, and every 5 years after injury through 2017. Results Age at injury has increased from 29 years in the 1970s to 42 years currently. This aging phenomenon was noted for all sexes, races, and etiologies except acts of violence. Although vehicular crashes continue to be the leading cause of SCI overall, injuries due to falls have increased over time particularly among those aged 46 years and older. Injuries resulting in tetraplegia are increasing while neurologically complete injuries are decreasing. Lengths of stay in the acute hospital and rehabilitation unit have declined. About 30% of persons with SCI are re-hospitalized during any given year following injury. Diseases of the genitourinary system are the leading cause of re-hospitalization. Mortality rates are significantly higher during the first year after injury. The life expectancy has improved but remain significantly below life expectancies of persons without SCI. The causes of death that have the greatest impact on reduced life expectancy over the last 5 decades are pneumonia and septicemia. Conclusion Study findings call for geriatrics expertise in the care for SCI and also highlights the need for a multi-dimensional risk assessment and intervention to reduce falls and SCI in older adults. Within the prevalent population, those who survive many years typically will have less severe injuries, high levels of independence and overall good health. Keywords Spinal cord injury; Epidemiology; Trends Disclosure of interest The authors declare that they have no competing interest. https://doi.org/10.1016/j.rehab.2018.05.542 ISPR8-1700
Clinical efficacy of upper limb robotic therapy in cervical spinal cord injured patients: A randomized control trial Z.A. Han 1,∗ , J. Kim 2 , H.J. Lee 1 , H.R. Kim 1 , D.Y. Cho 3 , B.S. Lee 1 , J. Kim 1 , J.E. Lim 3 , H.Y. Kim 3 1 National rehabilitation center, spinal cord injury rehabilitation, Seoul, Republic of Korea 2 National rehabilitation center, rehabilitation, Seoul, Republic of Korea 3 National rehabilitation center, Assistive technology, Seoul, Republic of Korea ∗ Corresponding author. E-mail address: [email protected] (Z.A. Han) Introduction/Background The efficacy of upper limb robotic therapy (UERs) in cervical SCI patients is relatively limited. With a better understanding of the effect of UER in cervical SCI patients, development of therapy programs with more adequate dosing, method, and safe protocols along with valid assessment tools will be possible in the future. This study evaluates the potential