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Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report.

ABSTRACT: INTRODUCTION:Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) and induces plastic changes in the human corticospinal tract. We have previously shown that PAS consisting of TMS pulses given at 100% of stimulator output and high-frequency PNS is beneficial for motor rehabilitation of patients with a chronic incomplete spinal cord injury (SCI). The therapeutic possibilities of this PAS variant for walking rehabilitation of paraplegic patients are unexplored. CASE PRESENTATION:A 47-year old man with traumatic incomplete paraplegia (AIS D, neurological level T7) received PAS to his left leg for 3 months at 12 months post injury (PAS1) and for an additional 3 months at 24 months post injury (PAS2). The right leg had normal AIS scores and was not stimulated. Before PAS, the patient was nonambulatory, could not stand without weight support, and was consequently not eligible for conventional walking rehabilitation. After PAS1, the patient could stand for 1.5?min and take 13 steps (24 steps in follow up) on parallel bars without weight support and was enrolled into conventional walking rehabilitation. He achieved independent walking ability with a rollator. During PAS2, walking distance increased 2.4 times faster than during the preceding year. The left leg AIS score and spinal cord independence measure mobility subscore increased. No adverse effects were detected. DISCUSSION:This is the first report of PAS with a high-frequency peripheral component that enabled and promoted walking rehabilitation. Together with previous reports on this technique, this result encourages further research into its therapeutic potential and mechanism.

SUBMITTER: Shulga A

PROVIDER: S-EPMC7426433 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report.

Shulga A A Savolainen S S Kirveskari E E Mäkelä J P JP

Spinal cord series and cases 20200813 1

<h4>Introduction</h4>Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) and induces plastic changes in the human corticospinal tract. We have previously shown that PAS consisting of TMS pulses given at 100% of stimulator output and high-frequency PNS is beneficial for motor rehabilitation of patients with a chronic incomplete spinal cord injury (SCI). The therapeutic possibilities of this PAS variant for walking ...[more]

PMID: 32792474

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Project description:ObjectiveTo determine whether neurophysiological mechanisms indicating cortical excitability, long-term potentiation (LTP)-like plasticity, GABAergic and glutamatergic function are altered in patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response.MethodsNeurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 ± 11 years; 30 females) and age/gender-matched healthy controls (n = 27, 28.5 ± 10 years; 25 females) were performed using transcranial magnetic stimulation-derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP-like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging.ResultsPAS-induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor-evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS-induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = -0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow-up assessments were available in six patients and demonstrated parallel improvement of PAS-induced plasticity and mRS.InterpretationAssessment of PAS-induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well-tolerated "electrophysiological biomarker" to monitor therapy response in the future.Clinical trial registrationClinicalTrials.gov: Identifier: NCT01865578.

Project description:Advances in our understanding of neural plasticity have prompted the emergence of neuromodulatory interventions, which modulate corticomotor excitability (CME) and hold potential for accelerating stroke recovery. Endogenous paired associative stimulation (ePAS) involves the repeated pairing of a single pulse of peripheral electrical stimulation (PES) with endogenous movement-related cortical potentials (MRCPs), which are derived from electroencephalography. However, little is known about the optimal parameters for its delivery. A factorial design with repeated measures delivered four different versions of ePAS, in which PES intensities and movement type were manipulated. Linear mixed models were employed to assess interaction effects between PES intensity (suprathreshold (Hi) and motor threshold (Lo)) and movement type (Voluntary and Imagined) on CME. ePAS interventions significantly increased CME compared to control interventions, except in the case of Lo-Voluntary ePAS. There was an overall main effect for the Hi-Voluntary ePAS intervention immediately post-intervention (p = 0.002), with a sub-additive interaction effect at 30 min' post-intervention (p = 0.042). Hi-Imagined and Lo-Imagined ePAS significantly increased CME for 30 min post-intervention (p = 0.038 and p = 0.043 respectively). The effects of the two PES intensities were not significantly different. CME was significantly greater after performing imagined movements, compared to voluntary movements, with motor threshold PES (Lo) 15 min post-intervention (p = 0.012). This study supports previous research investigating Lo-Imagined ePAS and extends those findings by illustrating that ePAS interventions that deliver suprathreshold intensities during voluntary or imagined movements (Hi-Voluntary and Hi-Imagined) also increase CME. Importantly, our findings indicate that stimulation intensity and movement type interact in ePAS interventions. Factorial designs are an efficient way to explore the effects of manipulating the parameters of neuromodulatory interventions. Further research is required to ensure that these parameters are appropriately refined to maximise intervention efficacy for people with stroke and to support translation into clinical practice.

Project description:Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cognition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China (approval No. TJ-A20151102) on July 11, 2015.

Project description:BackgroundAt present, the use of repetitive transcranial magnetic stimulation (rTMS) for generalized anxiety disorder (GAD) is limited to single-site interventions. We investigated whether dual-site frontoparietal stimulation delivered using cortical-cortical paired associative stimulation (ccPAS) had stronger clinical efficacy than single-site stimulation in patients with GAD.MethodsWe randomized 50 patients with GAD to 1 Hz rTMS (10 sessions) using 1 of the following protocols: single-site stimulation over the right dorsolateral prefrontal cortex (dlPFC; 1500 pulses per session); single-site stimulation over the right posterior parietal cortex (PPC; 1500 pulses per session); repetitive dual-site ccPAS (rds-ccPAS) over the right dlPFC and right PPC with 1500 pulses per session (rd-ccPAS-1500); or rds-ccPAS over the right dlPFC and right PPC with 750 pulses per session (rd-ccPAS-750). Both rds-ccPAS treatments used a between-site interval of 100 ms.ResultsClinical scores for anxiety, depression and insomnia were reduced in all 4 groups after treatment. We found greater improvements in anxiety symptoms in the rds-ccPAS-1500 group compared to the rds-ccPAS-750 and single-site groups. We found greater improvements in depression symptoms and insomnia in the rds-PAS-1500 group compared to the single-site groups. The rds-ccPAS-1500 group also showed significant or trend-level improvements in anxiety symptoms and insomnia at 10-day and 1-month followup. More patients responded to treatment with rds-ccPAS-1500 than with single-site stimulation. The between-group differences in response rates persisted to the 3-month follow-up. Treatment using rds-ccPAS with a between-site interval of 100 ms induced a more significant improvement than the between-site interval of 50 ms we evaluated in a previous study.LimitationsThese results need to be replicated in a larger sample using sham control and equal-pulse single-site stimulation.ConclusionFrontoparietal rds-ccPAS may be a better treatment option for GAD.

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Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report.

Publications

Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report.

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