Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Sex hormones, menstrual cycle
Brief summary
Emerging evidence indicates that females with MS experience worsened symptoms during the luteal phase (post ovulation) of the menstrual cycle when progesterone levels rise and estradiol fluctuate. The rapid hormonal swings may disrupt hypothalamic regulation, leading to an increase in body temperature - a well-established trigger for MS symptom exacerbation. These hormonal changes could also affect neuromuscular function, as estradiol and progesterone receptors are present in the nervous system and skeletal muscles. Three critical aspects of motor rehabilitation are corticospinal excitability, motor learning, and fatigability. Previous research indicates that corticospinal excitability and the capacity to learn fine motor tasks fluctuate across menstrual cycles, indicating hormonal influences on neuroplasticity. However, it remains unclear how these hormonal fluctuations specifically affect corticospinal excitability, motor learning, and motor fatigability in females with MS. Understanding these relationships could significantly improve rehabilitation approaches. For example, pre-menopause females with MS may experience a more optimal state for neuroplasticity during the follicular phase of their cycles, therefore providing a potential window for greater rehabilitation efficacy.
Detailed description
The objective of this project is to systematically examine how hormonal fluctuations pre-menopause influence corticospinal excitability, motor learning, and motor fatigability in females with MS. The study is structured around the following specific aims: Aim 1: Quantify the effects of estradiol and progesterone levels on corticospinal excitability in pre- menopausal females with MS. We will elicit motor evoked potentials by cortical and subcortical stimulation of corticospinal axons using transcranial magnetic stimulation (TMS). Aim 2: Evaluate how hormonal fluctuations across menstrual phases impact motor learning ability in pre-menopause females with MS. Participants will be asked to perform a finger sequence motor learning task using visual feedback. The task will be performed using a computer keyboard. Participants will be asked to copy the numerical sequence on a monitor in front of them that pertains to a number on the keyboard with their fingers. Participants will be given three different sequences with equivalent difficulty at each session to avoid carry-over effects between visits. Aim 3: Determine the relationship between hormonal fluctuations and motor fatigability in pre-menopause females with MS. Participants will perform a maximal voluntary force (MVF). Participants will then be asked to pinch to 80% of their MVF, and maintain this hold for as long as possible1. The trial will end when the force drops below 40% MVF. Two trials in total will be performed. Average time to fatigue (40% MVF) and slope of the drop-off will be calculated as a measure of overall fatigue.
Interventions
None listed
Sponsors
Milap Sandhu
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Diagnosis of relapsing-remitting, primary progressive or secondary progressive MS with no minimum years since diagnosis * Stable disease modifying therapies for at least 6 months * Eumenorrheic females
Exclusion criteria
* Another diagnosis (e.g., peripheral neuropathies or orthopedic) * Pregnancy as confirmed by urine test * Irregular menstrual cycles * Diagnosis of premenstrual dysphoric disorder or polycystic ovary syndrome * Taking antipsychotic medications / does not pass the TMS safety checklist
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Corticospinal excitability | At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal | Measuring the brain to muscle connection using transcranial magnetic stimulation - a non-invasive way to measure brain activity. Peak to Peak amplitude in mV is recorded |
| Blood Draw | At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal | To quantify estradiol and progesterone levels. Normative values of estradiol (E) and progesterone (P) per phase: early follicular (E: 125pmol/L; P: 0.38nmol/L), late follicular (E: 464pmol/L; P: 0.188nmol/L), luteal (E: 412pmol/L; P: 28.8nmol/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| strength | At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal | Measured by a pinch maximal voluntary contraction in lb-f |
| Fatigue | At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal | Measured with a pinch fatiguing task to estimate how quickly muscle of the hand fatigues. Measured in Seconds |
| Motor Learning | At 3 points during the individual's 1-month menstrual cycle, 1) Early Follicular 2) Late Follicular 3) Luteal | A visuomotor tracking task to measure difference between target trace and performed trace, measured in root mean squared error |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMilap Sandhu, PT, PhD
Shirley Ryan AbilityLab
Outcome results
None listed