Exploring the Use of Non-invasive Neuromodulation Combined With Exercise in People With Advanced Multiple Sclerosis (MS)
Exploring the Use of Non-invasive Neuromodulation Combined With Exercise in People With Advanced Multiple Sclerosis (MS)
The investigators hypothesis is that electrical stimulation to the tongue that directly
 stimulates two cranial nerve nuclei (Trigeminal and Facial Nerve Nuclei), will excite neural
 impulses to the brainstem and cerebellum. The investigators call this cranial nerve
 non-invasive neuromodulation (CN-NINM). The activation of these structures induces
 neuroplasticity when combined with specific physical exercises, can reduce symptoms of
 advanced MS, targeting primarily postural stability (sitting and standing), upper extremity
 movement, and ability to perform self-transfers.
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.