Exploring the Use of Non-invasive Neuromodulation Combined With Exercise in People With Advanced Multiple Sclerosis (MS)

The intervention will be similar to that used in the investigators previous work with
movement disorders, and will be tailored to the address issues unique to individuals with
advanced MS.

The study will enroll a total of 6 subjects having advanced MS that present with significant
seated and standing balance, posture, or movement control deficits due to MS.

Subjects will complete twice-daily lab training for two weeks (5 days/week). Each lab
training (morning and afternoon) includes 1.5 to 2 hours of instruction in balance, posture
and gait activities; therapeutic exercise for isolated muscle control; transfer training; and
relaxation training.

Activities are performed in 20-minute sessions with concomitant electrical stimulation of the
tongue. The intervention is customized according to each subject's particular symptoms and
tolerance. If a subject is not able to perform this amount of training, the training will be
adapted to a level that is tolerable.

After these 2 weeks, subjects will continue to perform these same intervention activities at
home for 4 weeks. They will return to the lab for 1 week of training and testing, then
perform home training for 4 weeks. This cycle is repeated for a total of 5 cycles.

After the 6 months have been completed, subjects may choose to participate in an optional
second phase of the study. The second phase includes an additional 12 months of participation
in which subjects perform the intervention activities at home training and return to the lab
on time per month for 2 hours of testing and 2 hours of training.

If successful, this study would indicate that CN-NINM intervention may reduce the symptoms of
advanced MS.

Inclusion Criteria:

- Subjects must be age 18 or older.

- Subjects will have a score between 6.5 to 7.5 on the Kurtzke Expanded Disability
Status Scale (EDSS). The EDSS is a method of quantifying disability in people with
multiple sclerosis.

- Score of 6.5: needs constant bilateral support to walk 20 meters without resting.

- Score of 7.0: unable to walk beyond five meters even with aid, and is essentially
restricted to a wheelchair; wheels self and transfers alone, and is active in
wheelchair about 12 hours a day.

- Score of 7.5: unable to take more than a few steps and is restricted to
wheelchair, and may need aid to transfer; wheels self, but may require a
motorized chair for a full day's activities.

- Subjects will have reached a plateau in an MS focused physical rehabilitation program
in the 6 months prior to enrollment.

- Requiring prior physical therapy will ensure that subjects have a core level of
function that will allow them to participate in the study.

- Requiring that subjects have reached a plateau will ensure that subjects'
response to the intervention is due to the use of the device and not to the
physical exercises alone.

- Subjects who have participated in a physical rehabilitation program demonstrate
that they are willing and able to commit to a rigorous training regimen.

- Subjects will have a maximum score of 20 on the Trunk Impairment Scale (TIS). The TIS
assesses static dynamic sitting balance and trunk coordination in a sitting position.
A score of 20 or lower indicates that their ability to adequately maintain sitting
posture is affected.

- Subjects may have upper extremity involvement.

- Subjects may have additional symptoms of nystagmus, dysarthria, sensory disturbance,
pain, and/or bowel and bladder function. As they present, we will use appropriate
assessments at baseline and successive study test points.

- Subjects are their own legal guardians, and are able to understand and give informed
consent.

Exclusion Criteria:

Subjects will have no major co-morbidities, especially neurological disorders, uncontrolled
pain, hypertension or diabetes. All subjects, if on medications, will not have had any
major changes in type or dosage in within 3 months of enrollment. Additionally, candidates
will be excluded if they:

- have Functional Systems Scores (FSS) 4 or greater for pyramidal, cerebellar,
brainstem, and sensory functions; 3 or greater for bowel and bladder function; and 2
or greater for cerebral function;

- are able to walk independently;

- use tobacco products (these activities tend to reduce tactile sensitivity in the oral
cavity);

- have any oral abrasions, cuts, cold sores, piercings, tissue inflammation, or have had
oral surgery within the previous 3 months;

- have a pacemaker, or are identified as at-risk for cardiovascular events;

- have a history of seizures;

- have a communicable disease;

- have a biomechanical prosthetic;

- are females who are pregnant.