Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0 mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion

Noninvasive reactivation of motor descending control after paralysis

© Mary Ann Liebert, Inc. 2015. The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2-6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain-spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord

Preoperative medical treatment in Cushing's syndrome : frequency of use and its impact on postoperative assessment : data from ERCUSYN

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). Patients and methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results

Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0 mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion

Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0 mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion

Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0 mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion

Noninvasive reactivation of motor descending control after paralysis

© Mary Ann Liebert, Inc. 2015. The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2-6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain-spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord

Noninvasive reactivation of motor descending control after paralysis

© Mary Ann Liebert, Inc. 2015. The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2-6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain-spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord

Noninvasive reactivation of motor descending control after paralysis

© Mary Ann Liebert, Inc. 2015. The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2-6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain-spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord

Epidural Spinal Cord Stimulation Improves Motor Function in Rats With Chemically Induced Parkinsonism

© The Author(s) 2019. Background. Epidural stimulation of the spinal cord can reorganize and change the excitability of the neural circuitry to facilitate stepping in rats with a complete spinal cord injury. Parkinson’s disease results in abnormal supraspinal signals from the brain to the spinal cord that affect the functional capacity of the spinal networks. Objective. The objective was to determine whether epidural stimulation (electrical enabling motor control, eEmc) of the lumbosacral spinal cord can reorganize the spinal networks to facilitate hindlimb stepping of rats with parkinsonism. Methods. A unilateral 6-OHDA (6-hydroxydopamine) lesion of the nigrostriatal pathway was used to induce parkinsonism. Sham rats (N = 4) were injected in the same region with 0.1% of ascorbic acid. Stimulation electrodes were implanted epidurally at the L2 and S1 (N = 5) or L2 (N = 5) spinal levels. Results. The 6-OHDA rats showed severe parkinsonism in cylinder and adjusting step tests and were unable to initiate stepping when placed in a running wheel and dragged their toes on the affected side during treadmill stepping. During eEmc, the 6-OHDA rats initiated stepping in the running wheel and demonstrated improved stepping quality. Conclusion. Stepping was facilitated in rats with parkinsonism with spinal cord stimulation. The underlying assumption is that the normal functional capacity of spinal networks is affected by supraspinal pathology associated with Parkinson’s disease, which either generates insufficient or abnormal descending input to spinal networks and that eEmc can appropriately modulate spinal and supraspinal networks to improve the motor deficits