Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary Progressive
Conditions
Keywords
multiple sclerosis, plasticity, electrical stimulation, NMES, modalities, neuroplasticity, motoneuron, aih, hypoxia, acute intermittent hypoxia, control, control group
Brief summary
The purpose of this study is to examine how neuromuscular electrical stimulation (NMES), may synergistically enhance corticospinal excitability in people with relapsing form multiple sclerosis (MS). This is an important intermediate step to evaluate the potential of AIH + NMES as a plasticity-priming strategy for more efficacious interventions for persons with MS. This study will measure ankle torque generation and amplitude of motor evoked potentials (MEPs) using a repeated measures study design in order to better understand the effects of AIH combined with NMES, as compared to only receiving NMES, and only receiving AIH.
Detailed description
NMES: NMES refers to the application of mild electrical stimulation and is often used as an assistive technology for foot drop in MS and other neurologic conditions. The NMES-induced improvement in motor performance appears to be mediated primarily by an increase in corticomotoneuronal excitability. A single session of NMES applied over a peripheral nerve, has been shown to transiently increase net corticospinal excitability (increased MEP amplitude) in both able-bodied individuals and in people with neurological conditions. AIH: AIH involves breathing brief bouts of low levels of oxygen. Research has found AIH to be a safe and effective intervention resulting in increased ankle strength in people with MS. While AIH has shown potential in enhancing neuroplasticity in people with spinal cord injury (SCI), it has yet to be studied extensively in MS. Preliminary research in the MS population demonstrates that a single session of AIH enhances motor output, increasing voluntary muscle strength by as much as 15-20% within 60 minutes. Over the past decade, studies have found AIH can rapidly enhance neural plasticity in persons with incomplete SCI. AIH activates the serotonergic pathway, leading to increased activity of serotonin receptors and the synthesis of plasticity-related proteins. This plasticity is manifested by a rapid increase in voluntary muscle strength, emerging within 60-90 minutes. In this study, the investigators will examine how NMES, which has been shown to affect cortical excitability, and AIH, which has been shown to affect corticospinal plasticity, may synergistically enhance corticospinal excitability in people with relapsing form of MS. Foot drop is a common symptom in the diagnosis of MS where the inability to maintain active dorsiflexion during the swing phase of the gait cycle affects walking efficiency, instability, and falls. Seminal studies show that individuals with MS retain the ability to express plasticity even at higher levels of disease burden. This indicates that strategies targeting neuroplasticity can be used to enhance functional recovery and limit the impact of MS disability. The investigators will conduct a randomized, blinded, placebo-controlled, cross-over study in 20 MS patients with established motor deficits and controlled relapse activity and 20 control subjects with no neurological diagnosis.
Interventions
During AIH, the participant will be equipped with a non-rebreathing face mask, and provided with the AIH intervention. The AIH intervention involves alternating breathing cycles. One cycle involves breathing air with lower oxygen concentration (9-10% oxygen) for 30 and 90 seconds, followed by breathing normal room air (21% oxygen) for a similar duration. This cycle is repeated 15 times in one session. Blood oxygen and heart rate are monitored throughout.
OTHERNeuromuscular Electrical Stimulation
During NMES, participants will receive electrical stimulation to the common peroneal nerve. Stimulation will be done with a 50% duty cycle, duration of 0.5-1ms for each pulse and a frequency 25-40 Hz. The stimulus intensity will be adjusted to produce approximately 50% of the maximum M-wave (compound muscle action potential) for each participant.
Sponsors
Shirley Ryan AbilityLab
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
randomized, blinded, cross-over study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
for persons with MS: * Diagnosis of relapsing form of MS * Expanded Disability Status Scale (EDSS) score of at least 3 and no more than 6.5 * Relapse free for at least 1 year * Age ≥18 years and ≤75 years * No change in Dalfampridine dose at least 2 months prior to enrollment
Exclusion criteria
for persons with MS: * Uncontrolled hypertension or hypotension (outside 140/90 and 90/60 mmHg) * History of epilepsy or seizures Inclusion Criteria for uninjured controls: * Age ≥18 years and ≤75 years * Safe to participate in TMS (TMS questionnaire)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motor Evoked Potentials (MEPs) in Ankle Dorsiflexors | Immediately prior to and within 60 minutes after the intervention. | The MEPs will be elicited by Transcranial Magnetic Stimulation (TMS), a procedure that uses magnetic fields to stimulate nerve cells in the brain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ankle Dorsiflexion Torque | Immediately prior to and within 60 minutes after the intervention. | Maximal volitional ankle dorsiflexion flexion torque will be measured using a strength testing dynamometer (Biodex System 4). |
| Ankle Dorsiflexion EMG | Immediately prior to and within 60 minutes after the intervention. | While measuring ankle dorsiflexion torque, the investigators will also record surface electromyography (EMG) from the tibialis anterior muscle during each contraction. Average peak EMG amplitude will be calculated. |
| Symbol Digit Modalities Test | Immediately prior to and within 60 minutes after the intervention. | A neurocognitive test that requires individuals to pair specific numbers with given geometric figures within 90 seconds. Both written and oral format will be administered, and scores will be calculated by totaling the number of correct answers for each section. |
Countries
United States
Outcome results
None listed