Case report
Open Access
Neuromuscular electrical stimulation and dietary interventions to
reduce oxidative stress in a secondary progressive multiple sclerosis
patient leads to marked gains in function: a case report
David Reese1,2, Ezzatolah T Shivapour3, Terry L Wahls4,5,6*, Shauna D
Dudley-Javoroski2 and Richard Shields2
Addresses: 1Performance Therapies, PC, Ridgeway Drive, Coralville, Iowa, USA
2Department of Physical Therapy, University of Iowa Carver College of Medicine, Iowa City, Iowa, 52246, USA
3Department of Neurology, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, Iowa, 52246, USA
4Veterans Administration (VA), Iowa City VA Medical Center, 601 Highway 6 West, Iowa City, Iowa, 52246, USA
5Center for Research in the Implementation of Innovative Strategies in Practice (CRIISP) VA HSR&D Center of Excellence, Iowa City
VA Medical Center, 601 Highway 6 West, Iowa City, Iowa, 52246, USA
6Division of General Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive,
Iowa City, Iowa, 52246, USA
Email: DR - DReese@perther.com; ETS - et-shivapour@uiowa.edu; TLW* - Terry.Wahls@va.gov; SDDJ - shauna-dudley@uiowa.edu;
RS - richard-shields@uiowa.edu
*Corresponding author
Received: 5 May 2009 Accepted: 17 July 2009 Published: 10 August 2009
Cases Journal 2009, 2:7601 doi: 10.4076/1757-1626-2-7601
This article is available from: http://casesjournal.com/casesjournal/article/view/7601
© 2009 Reese et al.; licensee Cases Network Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Neuromuscular electrical stimulation has been used to aid musculoskeletal recovery. Excessive
oxidative stress and excitoxicity are implicated in secondary progressive multiple sclerosis. A 52-
year-old white female with SPMS had been scooter- and cane-dependent for 4 years. She requested
and received a trial of neuromuscular electrical stimulation. Two months after initiating NMES the
patient adopted several nutritional interventions to lower oxidative stress and excito-toxicity. During
the first 2 months of neuromuscular electrical stimulation, the therapist observed modest gait
improvements. Following the addition of nutritional interventions, more rapids gains in strength and
endurance, including muscle groups not receiving neuromuscular electrical stimulation were
observed by both the therapist and the patient. After 8 months of neuromuscular electrical
stimulation (6 months of nutritional intervention) the patient’s function had improved sufficiently that
she no longer used a scooter or cane and rode her bicycle routinely 8 miles, including hills.
Introduction
The majority of those with relapsing remitting multiple
sclerosis (MS) will go onto secondary progressive MS
(SPMS) within 15 years of diagnosis. Neurodegeneration
has been the presumed cause of the accumulating
disability and loss of function [1].
Neuromuscular electrical stimulation (NMES) has been used
to speed recovery after stroke [2]. Nutritional supplements
and dietary interventions aimed at reducing oxidative stress
and excito-toxicity are thought be benefit patients with MS
[3,4]. Reduction of intracellular oxidative stress is associated
with neuroprotection in experimental optic neuritis [5].
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In this article we describe the use of physical therapy (PT),
NMES-augmented exercises, and nutritional interventions
in a patient with SPMS.
Case presentation
A 52-year-old white female physician (tw) with secondary
progressive multiple sclerosis (SPMS) was referred to
physical therapy for evaluation and treatment of low back
pain and gluteus pain. She had been diagnosed with MS in
2000. In 2003 her disease was reclassified as SPMS, at
which time she started using a cane and an ankle foot
orthotic (AFO) for left (L) foot drop. In 2004 she began
using a scooter for fatigue. At presentation ambulation was
limited to short distances (<20 yards). She sat semi-
recumbent in a zero gravity chair for meals and desk work
because of back fatigue. Stumbles and near falls were more
likely to occur late in the day. Her MS medications
included B complex vitamins, carnitine, lipoic acid,
gabapentin, bupropion, baclofen, modafanil, mycophe-
nolate, tolterodine, and minocycline. Bilateral glutei pain
was reported. Low back pain (LBP) was centrally located
and gradually progressed into the mid-thoracic region by
evening. Pain was rated at 5 out of 10 for both.
PT notes indicated the presence of atrophy of her left lower
extremity and glutei muscles. Her gait with a cane but
without the AFO demonstrated a left foot slap during
stance phase. Manual muscle tests revealed diffuse
weakness of the core and lower extremities with left
significantly weaker than right. Strength was rated 3 out of
5 for core muscles and left tibia anterioralis and 4 out of 5
for left hamstrings and quadriceps. Pain was attributed to
abnormal posture and gait due to neuromuscular weak-
ness. Patient and therapist goals were to increase strength
and flexibility, and thereby improve safety and diminish
pain. Prognosis was rated as fair.
Intervention
After 3 months of usual PT care-stretching and core
strengthening, utilizing both clinic sessions and a home
exercise program (HEP)-the patient expressed a desire to
try neuromuscular electrical stimulation (NMES). A test
session was completed to confirm patient tolerance and
capability of independent operation of the device. The
patient was instructed to use a volitional muscle contrac-
tion along with the induced muscle contraction during
NMES session (Table 1). The current, in milliamps, was
increased within the patient tolerance for discomfort to
attain a tetanic contraction in addition to her volitional
contraction. Immediately following NMES the patient
reported an enhanced sense of well-being following
NMES. She also reported that unlike exercise, the NMES
did not result in perceived muscle fatigue or generalized
fatigue. A portable electrotherapy system 300 PV® manu-
factured by Empi was then acquired for home use. The
patient was advised that an NMES time of 45 min per day
was required to build muscle strength and 15 min per day
was required for strength maintenance. She should use
NMES on her abdominals and paraspinous muscle groups
while completing her lumbar strengthening HEP. She
could train additional muscle groups (using isometric
volitional muscle contractions) as her schedule allowed.
Two months following initiation of NMES, the patient
reported that she had made multiple nutritional interven-
tions to reduce oxidative stress and excito-toxicity (based
upon her review of the medical literature). Her typical
daily intake included 600 grams of cruciferous vegetables,
300 grams of brightly colored fruits or vegetables, and 60
to 100 grams of meat, poultry or fish, but no milk, eggs, or
gluten-containing grains. The patient also began the
following supplements: 2 g each of glutathione, N
acetyl-cysteine, and taurine daily, and lithium orotate
300 mg twice daily.
Five months following initiation of NMES, to facilitate
increasing both the number of minutes and muscle groups
receiving NMES, the patient acquired an eight-channel
electrotherapy unit, the TDR68® manufactured by Tone-
Amatic. The NMES protocol then consisted of 20 to
40 min of NMES to the upper and lower abdominals,
paraspinous, both gluteus, and left hamstrings, quad-
riceps, hip flexors, and tibia anterioralis muscle groups
eachmorning, in addition to four or more 30-min sessions
of NMES, using her portable device, while at work.
To assess interventions used and functional gains accrued
by the patient, we used patient reports of function and
average minutes per muscle group of electrotherapy, and
PT clinical notes. Because the patient had participated in
the North American Research Committee on Multiple
Sclerosis (NARCOMS) [6] patient registry since 2005, we
reviewed self-reported disability scales from her responses
to the NARCOMS quality of life questions before and
during the intervention.
Outcome
After 3 months of PT the patient’s back pain had
diminished, but ambulation and sitting endurance were
Table 1. Electrotherapy device initial settings
Device 300 PV®
PP1 large muscle Custom small muscle
Wave form symmetrical asymmetrical
Ramp on (seconds) 3 2
On time seconds) 12 5
Ramp off (seconds) 2
Off time 20 5
Pulse rate (Hz) 35 50
Pulse width 300 µ 400 µ
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unchanged. She could do no more than 10 minutes of her
HEP and still work due to fatigue limitations. However,
after 2 weeks of NMES, the patient could complete
15 min of NMES-augmented HEP twice daily without
difficulty. In addition the patient routinely completed
another 60 to 90 min of NMES (while at work) of the
abdominal, gluteus, and left anterior tibialis muscle
groups. At 6 weeks the patient reported improved
endurance for sitting and ambulation, although a cane
was still required. The therapist observed gains in
endurance and strength.
Within 2 weeks of initiating dietary interventions, the
patient reported singing for the first time in 6 months. The
therapist noted an increased rate of improvements in her
strength and endurance, including muscles groups not
receiving electrotherapy. The number of minutes and
number of muscle groups were increased gradually. Four
months following initiation of NMES the patient routinely
did 30 minutes of NMES while completing her home
exercise program each day and another 4 to 5 hours of
NMES at much lower intensity through out the day while
working or at home. Five months following initiation of
NMES the patient stopped using her scooter, and 9months
after initiation of NMES the patient was able to bicycle 8
miles, including hills. One year following initiation of
NMES and nutritional interventions the patient routinely
rode her bicycle five miles to work.
The NARCOMS quality of life responses indicated
gradual worsening of MS-related symptoms and disabil-
ity scale prior to the intervention. Six weeks following
initiation of NMES, improvement in overall symptoms
and decreased fatigue were reported. Six months after
initiation of NMES improvements were noted in overall
MS symptoms, gait disability, and fatigue disability
(Table 2).
Discussion
A 52-year-old white female with SPMSwith 2 years of well-
documented, gradual worsening of MS-related symptoms
underwent NMES and dietary interventions to reduce
oxidative stress and excito-toxicity. The patient experi-
enced improved strength and endurance in response to
the NMES. Following the dietary changes, the rate of
improvements in function were more accelerated. To our
knowledge this is the first published case report of the use
of a NMES-augmented HEP and intensive nutritional
support in a patient with progressive multiple sclerosis
that resulted in significant reversal of disability.
The mechanisms by which NMES results in functional
gains were likely due to changes both within the central
nervous system (CNS) and the muscle. Physical activity
has been associated with increases in nerve growth factor,
brain-derived neurotrophic growth factor (BDNF), insu-
lin-like growth factor, and glial growth factor [7,8].
Increased consumption of micronutrients appeared to have
been synergistic with NMES. CNS response to circulating
neurotrophins is dependent on the availability of intracel-
lular adenosine triphosphate (ATP). Facilitating more
effective mitochondrial bio-energetics with riboflavin, nia-
cinamide, ubiquinone, and more antioxidants, could have
facilitated enhanced responsiveness to neurotrophins, per-
haps increasing dendritic sprouting and myelin generation.
Excessive neuronal excitation is present in experimental
autoimmune encephalitis and patients with an acute MS
relapse, primary progressive MS, and SPMS [9,10].
Blocking glutamate synthesis with taurine, glutathione,
and N acetyl cysteine lowers excito-toxicity and has
reversed axonal loss and disability in mice [11]. Antiox-
idants from food and nutritional supplements have been
shown to inhibit T cell migration [12], block excito-
toxicity [13], decrease oxidative stress [14] in both
experimental autoimmune encephalitis and in multiple
sclerosis patients.
Conclusion
NMES and dietary manipulation aimed at reduction of
oxidative stress and excito-toxicity in a patient with a
4-year history of SPMS was associated with large gains in
patient function. This case suggests that the nutritional
intervention and NMES were synergistic. Whether either
NMES alone or nutrition alone would have yielded as
many functional gains is unknown. Additional pilot
studies are warranted to determine if these effects can be
replicated. Careful patient selection criteria will be
required to identify individuals capable of complying
Table 2. NARCOMS survey questions and patient responses
Date questions answered 11/23/
2005
6/2/2006 11/28/
2006
5/5/2007 12/12/20071 4/30/20082
Compare your overall MS symptoms now with
what you experienced 6 months ago. Is your MS:
Worse Worse Worse Worse Somewhat Better Much Better
Rate your MS symptoms overall Moderate Moderate Moderate Moderate Minimal None
Fatigue symptoms Moderate Severe Total Total Moderate Mild
1Six weeks after initiation of NMES.
2Six months after initiation of NMES and 4 months after nutritional intervention.
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with these interventions because of the substantial time
commitment to complete the NMES sessions, tolerance for
discomfort without immediate benefit, and commitment
to what may be substantial changes in dietary habits.
Patient perspective
I had experienced gradual worsening of MS related
symptoms since the diagnosis in 2000. It had been my
expectation that continued worsening of my disability was
inevitable. Following 18 months of neuromuscular
electrical stimulation and intensive nutrition I can now
bicycle 5 miles to work each day. I have noted when I am
unable to eat 600 grams of cruciferous vegetables as when
traveling, within 48 hours I experience subjective decline
in energy and mental focus. When my electrical therapy
device has had to be repaired and I have been without
electrical stimulation for 48 hours I also experienced
subjective decline in energy. It is my perception that two
modalities (electrical therapy and antioxidant rich food
and supplements) have additive, if not synergistic benefit
to my recovery.
Abbreviations
AFO, ankle foot orthotic; ATP, adenosine triphosphate;
CNS, central nervous system; HEP, Home exercise program;
LBP, Low back pain; NARCOMS, North American Research
Committee on Multiple Sclerosis; NMES, neuromuscular
electrical stimulation; PT, physical therapy; SPMS, second-
ary progressive multiple sclerosis.
Consent
Written informed consent was obtained from the patient
for publication of this case report and accompanying
tables. A copy of the written consent is available for review
by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
RD, SE and WT reviewed the clinical notes and wrote the
article. DS and SR reviewed the manuscript and assisted
with identifying additional references related to the use of
neuromuscular electrical stimulation. All authors reviewed
and approved the article content.
Acknowledgements
No financial support to this project was received other
than in-kind support from the Center for Research in the
Implementation of Innovative Strategies in Practice
(CRIISP) VA HSR&D Center of Excellence, at the Iowa
City VA Medical Center, Iowa, USA.
References
1. Hampton DW, Anderson J, Pryce G, Irvine KA, Giovannoni G,
Fawcett JW, Compston A, Franklin RJ, Baker D, Chandran S: An
experimental model of secondary progressive multiple
sclerosis that shows regional variation in gliosis, remyelina-
tion, axonal and neuronal loss. J Neuroimmunol 2008, 201-
202:200-211.
2. Daly JJ, Roenigk K, Holcomb J, Rogers JM, Butler K, Gansen J,
McCabe J, Fredrickson E, Marsolais EB, Ruff RL: A randomized
controlled trial of functional neuromuscular stimulation in
chronic stroke subjects. Stroke 2006, 37:172-178.
3. Gonsette RE: Oxidative stress and excitotoxicity: a therapeutic
issue in multiple sclerosis? Mult Scler 2008, 14:22-34.
4. Syburra C, Passi S: Oxidative stress in patients with multiple
sclerosis. Ukr Biokhim Zh 1999, 71:112-115.
5. Qi X, Lewin AS, Sun L, Hauswirth WW, Guy J: Suppression of
mitochondrial oxidative stress provides long-term neuropro-
tection in experimental optic neuritis. Invest Ophthalmol Vis Sci
2007, 48:681-691.
6. Marrie RA, Cutter G, Tyry T, Campagnolo D, Vollmer T: Validation
of the NARCOMS registry: diagnosis. Mult Scler 2007, 13:770-
775.
7. Gold SM, Schulz KH, Hartmann S, Mladek M, Lang UE, Hellweg R,
Reer R, Braumann KM, Heesen C: Basal serum levels and
reactivity of nerve growth factor and brain-derived neuro-
trophic factor to standardized acute exercise in multiple
sclerosis and controls. J Neuroimmunol 2003, 138:99-105.
8. Toldy A, Stadler K, Sasvári M, Jakus J, Jung KJ, Chung HY, Berkes I,
Nyakas C, Radák Z: The effect of exercise and nettle
supplementation on oxidative stress markers in the rat
brain. Brain Res Bull 2005, 65:487-493.
9. Sarchielli P, Greco L, Floridi A, Floridi A, Gallai V: Excitatory amino
acids and multiple sclerosis: evidence from cerebrospinal
fluid. Arch Neurol 2003, 60:1082-1088.
10. Vercellino M, Merola A, Piacentino C, Votta B, Capello E,
Mancardi GL, Mutani R, Giordana MT, Cavalla P: Altered glutamate
reuptake in relapsing-remitting and secondary progressive
multiple sclerosis cortex: correlation with microglia infiltra-
tion, demyelination, and neuronal and synaptic damage.
J Neuropathol Exp Neurol 2007, 66:732-739.
11. Basso AS, Frenkel D, Quintana FJ, Costa-Pinto FA, Petrovic-
Stojkovic S, Puckett L, Monsonego A, Bar-Shir A, Engel Y, Gozin M,
Weiner HL: Reversal of axonal loss and disability in a mouse
model of progressive multiple sclerosis. J Clin Invest 2008,
118:1532-1543.
12. Marracci GH, McKeon GP, Marquardt WE, Winter RW, Riscoe MK,
Bourdette DN: Alpha lipoic acid inhibits human T-cell migra-
tion: implications for multiple sclerosis. J Neurosci Res 2004,
78:362-370.
13. Kobayashi MS, Han D, Packer L: Antioxidants and herbal extracts
protect HT-4 neuronal cells against glutamate-induced
cytotoxicity. Free Radic Res 2000, 32:115-124.
14. van Meeteren ME, Teunissen CE, Dijkstra CD, van Tol EA:
Antioxidants and polyunsaturated fatty acids in multiple
sclerosis. Eur J Clin Nutr 2005, 59:1347-1361.
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