Effects of a Novel Therapeutic Intervention in
Patients With Diabetic Peripheral Neuropathy
Adel Alshahrani, DSc,
Mark Bussell, DPT,
Eric Johnson, DSc,
Bryan Tsao, MD,
Khalid Bahjri, MD
School of Allied Health Professions, Department of Physical Therapy, Loma Linda University, Loma Linda, CA;
Rehabilitation Services, Department of Physical Therapy, Loma Linda University Medical Center, Loma Linda, CA;
Neurology Department, Loma Linda University School of Medicine, Loma Linda, CA;
School of Public Health, Department of Public Health,
Loma Linda University, Loma Linda, CA.
Objective: To determine the effect of a novel therapeutic intervention called intraneural facilitation on balance measures and a neuropathy scale
in patients with diabetic peripheral neuropathy.
Design: Prospective pre- and posttest, single group clinical trial.
Setting: Outpatient physical therapy clinic.
Participants: Patients with diabetic peripheral neuropathy (NZ13).
Intervention: Subjects received 10 sessions of intraneural facilitation.
Main Outcome Measures: The modiﬁed Total Neuropathy Scale, the NeuroCom SMART Balance Master system computerized dynamic
posturography (CDP) that includes the Sensory Organization Test (SOT) and the limits of stability (LOS), and the Activities-speciﬁc Balance and
Conﬁdence (ABC) scale.
Results: Subjects in this study showed signiﬁcant improvement in the modiﬁed Total Neuropathy Scale, SOT, and 1 component in the LOS test
(movement velocity). There were no signiﬁcant differences in the ABC scale or in 4 components of the LOS test, which were reaction time, end
point excursion, maximum excursion, and directional control.
Conclusions: Intraneural facilitation improved objective balance measures and neuropathy symptoms in patients with diabetic peripheral
neuropathy. Further study is needed to determine long-term beneﬁts of this intervention.
Archives of Physical Medicine and Rehabilitation 2016;-:-------
ª2016 by the American Congress of Rehabilitation Medicine
Diabetes mellitus (DM) is a common disorder affecting in-
dividuals in the United States and in the world.
The prevalence of
DM has increased noticeably over the last 3 decades with an
estimated 380 million people currently diagnosed with the dis-
DM is associated with numerous systemic complications
that effect the retina, heart, brain, kidneys, and nerves.
The most common symptomatic complication of DM is dia-
betic peripheral neuropathy (DPN), estimated to occur in 50% of
patients with DM.
Despite therapeutic advances of diabetes care
over the last decade, there are few known interventions that
appropriately address the progression and treatment of DPN.
can occur in many forms, but it most commonly presents as a
painless sensorimotor distal symmetric polyneuropathy (DSPN).
Diabetic DSPN causes deterioration of the peripheral nervous
system in a length-dependent fashion and can negatively affect the
Impaired proprioceptive input renders these
patients more susceptible to loss of balance during static and
This can impair physical function by
reducing standing and walking activities because many patient
experience fear of falling.
The pathogenesis of DPN is multifactorial and mediated by
alterations in the polyol pathway, aldose reductase inhibitors,
advanced glycation products, disordered biochemistry conse-
quences, essential fatty acids, neurotrophic factors, and oxidative
stress. The common pathologic end point is endoneurial micro-
angiopathy and subsequent nerve ischemia and hypoxia.
such, patients with DPN are more likely to develop an array of
peripheral nerve disorders and balance problems and are at a
higher risk of falling.
0003-9993/16/$36 - see front matter ª2016 by the American Congress of Rehabilitation Medicine
Archives of Physical Medicine and Rehabilitation
journal homepage: www.archives-pmr.org
Archives of Physical Medicine and Rehabilitation 2016;-:-------
The current study used an innovative approach termed intra-
neural facilitation in the treatment of diabetic DSPN. This
approach aims to bias blood ﬂow into the neural fascicle, improve
endoneurial capillary circulation, and reverse intrafascicular
ischemia. This passive technique includes stretching muscles,
mobilizing joints, tractioning skin, distending visceral structures,
and distorting blood vessels to reroute blood to the ischemic
We sought to determine the effectiveness of intraneural
facilitation in DSPN using validated neuropathy scales, objective
static measures, dynamic balance measures, subjective balance
measures, and quantitative posturography balance measures.
This institutional review boardeapproved study was conducted at
Loma Linda University, which is a tertiary teaching hospital with
an outpatient physical therapy clinic providing care to a diverse
group of patients. Study subjects were screened from our clinic
between October 2014 and February 2015. Informed consent was
obtained, and the assessment and intervention procedures were
conducted in our physical therapy area.
Inclusion criteria for this study included the following: men
and women with DPN who were from 18 to 85 years of age,
DSPN form of DPN conﬁrmed by a medical doctor, and ability to
hold static balance for a minimum of 5 minutes.
Potential subjects were excluded if they had comorbidities (eg,
open wounds, cardiac disease, other forms of progressive neuro-
logic disease) or peripheral polyneuropathy affecting balance.
Modiﬁed Total Neuropathy Scale
The modiﬁed Total Neuropathy Scale is scored from 0 to 24 with
each neuropathy rated from 0 to 4 (0 being healthy and 4 being
severe neuropathy). The modiﬁed Total Neuropathy Scale severity
levels are divided into 3 levels: 0 to 8 (mild), 9 to 16 (moderate),
and 17 to 24 (severe). The clinical testing for the modiﬁed Total
Neuropathy Scale includes muscle strength, vibration sense, pin
sensation level, and muscle stretch reﬂexes.
Static and dynamic balance scales
The NeuroCom SMART Balance Master system
dynamic posturography (CDP) was used. This apparatus consists
of 2 forceplates that can be pitched up and down and in an
anterior-posterior plane. During this test, our subjects wore safety
harnesses and were supported by 2 researchers to minimize the
risk of falling. The subjects stood upright on the center of the
forceplates in a standardized position. In this machine, 2 tests
were used. The ﬁrst was the Sensory Organization Test (SOT),
which assesses 3 sensory systems that affect postural control
(visual, somatosensory, and vestibular). Six different conditions
are tested consecutively with three 20-second trials. In step 1 the
patient is required to stand still with eyes open (all sensory in-
formation available); in step 2 the patient is required to stand still
with their eyes closed; in step 3 the surround moves as the patient
moves; in step 4 the forceplate moves as the patient moves; in step
5 the patient closes their eyes and the forceplate moves as the
patient moves; and in step 6 the surround and forceplate move as
the patient moves. We assessed the composite equilibrium and
static balance scores.
The second was the limits of stability
(LOS) test, which quantiﬁes control of the center of gravity. The
patient is required to voluntarily sway in 8 directions without
losing their balance. The LOS test includes reaction time, move-
ment velocity, end point excursion, maximum excursion, and
directional control. We took the composite scores of reaction time,
movement velocity, end point excursion, maximum excursion, and
directional control from the 8 directions.
Activities-speciﬁc Balance Conﬁdence scale
The Activities-speciﬁc Balance Conﬁdence (ABC) scale
subjective measure of conﬁdence in performing several activities
without losing balance or suffering a sense of wobbliness. It is a
16-item self-report measure in which subjects rate their balance
conﬁdence for performing certain activities. Each item ranges
from 0 to 100. A score of zero implies falling, and a score of 100
implies patient’s conﬁdence of stability. The total score of this
scale is derived by adding all items together and then
dividing by 16.
The patients were ﬁrst assessed by a physician and determined to
have DPN. The physician then referred the patients to our clinic
for physical therapy using intraneural facilitation. At the start of
therapy, the patient was given the option to participate in the study
or to proceed with treatment without study participation. If the
patient chose to participate in the study, baseline data were
recorded from an initial CDP test, a modiﬁed Total Neuropathy
Scale assessment, and ABC balance scores. After the initial
assessment, the patient received intraneural facilitation for 10
treatments. On the 12th session, the baseline tests were repeated,
and follow-up data were recorded for analysis.
Pretreatment assessment included baseline demographic data, the
modiﬁed Total Neuropathy Scale, SOT and LOS test scores, and
the ABC scale.
Posttreatment data were collected for these same measures
after 10 sessions of intraneural facilitation treatment.
Data management and analysis
Two researchers conducted data management using coding man-
uals for all study measures. All study data were initially reviewed
to identify missing values. Methods for missing value adjustment
included imputation, list-wise deletion, or case-wise deletion. All
modiﬁcations were recorded in the data coding manual for future
missing data analysis.
List of abbreviations:
ABC Activities-speciﬁc Balance Conﬁdence
CDP computerized dynamic posturography
DM diabetes mellitus
DPN diabetic peripheral neuropathy
DSPN distal symmetric polyneuropathy
LOS limits of stability
SOT Sensory Organization Test
2 A. Alshahrani et al
Data were analyzed using SPSS Statistics 22.
Means and SDs
were calculated for the outcome measures separately pre- and
postintervention. Paired ttest was used to detect signiﬁcant change
in SOT, reaction time, movement velocity, end point excursion,
maximum excursion, and directional control between pre- and
postintervention. Wilcoxon signed-rank test was used to compare
differences in directional control and modiﬁed Total Neuropathy
Scale between pre- and postintervention. A Pvalue of <.05 was
Of 25 subjects screened for our study, 17 met inclusion criteria
and were enrolled. Of these, 13 completed the study (ﬁg 1). Four
subjects did not complete the study: 1 developed a foot infection,
1 had insurance problems that prevented ongoing therapy, and 2
elected to exit the study because of time restraints. Subject de-
mographics are listed in table 1.
The modiﬁed Total Neuropathy Scale showed signiﬁcant reduc-
tion from pre- and posttreatment measurements (PZ.001) (table 2).
For changes in the SOT, we found a signiﬁcant increase from pre- and
posttreatment measurements (PZ.012) (table 2). For the LOS test
components, the movement velocity showed a signiﬁcant increase
from pre -to posttreatment measurements (PZ.023) (table 2). The
remaining measures of reaction time, directional control, end point
excursion, maximum excursion, and the ABC scale showed a trend
toward improvement but did not show statistically signiﬁcant differ-
ences before or after intraneural facilitation (see table 2).
The results of our study are consistent with previous reports
indicating that patients with DSPN are more susceptible to falls
during static and dynamic conditions.
In addition, our re-
sults show that intraneural facilitation can improve neuropathy
symptoms as measured by the modiﬁed Total Neuropathy Scale
(PZ.001), static balance or SOT (PZ.012), and dynamic balance
or movement velocity (PZ.023) scores. All other LOS test
components (reaction time, directional control, end point excur-
sion, and maximum excursion) showed a trend toward posttreat-
ment improvement but were not statistically signiﬁcant. Medical
records indicating the degree of glycemic control were not
available to researchers for all subjects.
We chose to use the modiﬁed Total Neuropathy Scale in our
study because it was easy to use and is a valid tool.
been used extensively in the literature for different conditions as a
validated tool to measure static and dynamic balance.
ney et al
looked at the relation between falls history and CDP
scores. They found that scores <38 increased the likelihood ratio
for recognizing repeated fallers in the last 6 months. On subjects
with diabetes, Simmons et al
measured postural instability in 2
groups: those with or without cutaneous sensory discrepancies and
a control nondiabetic group. They found that CDP scores are less
for subjects with cutaneous sensory discrepancies; therefore, they
are more likely to have postural instability. In another study, Di
Nardo et al
found that CDP distinguished between subjects with
DM with and without peripheral neuropathy.
Although many interventions have tried to mitigate the effect
of DPN through exercises, it remains a progressive disease with
few effective interventions. There are few systematic physical
therapy approaches that are typically used in treating patients with
DPN. For instance, Kochman
studied the use of monochromatic
infrared energy plus strengthening, stretching, and balance exer-
cises on patients with DPN to improve balance. The author re-
ported improved balance and a reduction in the number of falls.
Mueller et al
investigated weight-bearing exercises versus none
weight-bearing exercises on patients with DPN. The weight-
bearing group revealed signiﬁcant improvement over the none
The effects of therapeutic rehabilitation on balance in patients
with DPN have included modalities,
combining modalities with
and assistive devices.
divided subjects into 2 groups. One group used a single-
point cane, and the other group did not use a cane. In the single
point cane group, they found a reduction in failure rate during
weight transfer to unipedal stance. Richardson et al
Fig 1 Subject screening and completion. Abbreviations: ABC, ac-
tivities of balance conﬁdence; INF, intraneural facilitation; LOS, limit
of stability; mTNS, modiﬁed total neuropathy scale; SOT, sensory or-
Table 1 Patient demographics (NZ13)
Demographic Minimum Maximum Mean SD Male Female
Age (y) 49 73 65.157.548
Sex (n) 7 6
Intraneural facilitation for neuropathy 3
subjects into 2 groups. One group received open and closed chain
ankle strengthening, wall slides, and single-leg stance, and the
other group received neck ﬂexion and scapular stabilization ex-
ercises. In the ankle exercises group, they found signiﬁcant im-
provements in tandem stance, single-leg stance, and functional
studied weight-bearing exercises versus none
weight-bearing exercises in patients with DPN. The
weight-bearing group showed signiﬁcance improvement over the
noneweight-bearing group in the 6-minute walk distance and
daily step counts. Exercise may play an important role in patients
with DPN. On the other hand, exercise usually needs weight
bearing and utilization of painful limbs. Also, recent studies
highly recommended minimal physical activity for patients with
DPN to prevent adverse events.
To decrease pain, paresthesia,
and lesions associated with DPN through physical therapy, we
should limit patients participating with exercise activities to
enhance functional outcomes.
The present study demonstrates
decreased neuropathic symptoms and improved balance using
intraneural facilitation. By reducing patient neuropathic symp-
toms, intraneural facilitation may enhance patient participation in
therapeutic exercise programs and form a bridge between the
inactive painful patient with diabetes and the active nonpainful
patient with diabetes who can exercise.
The intraneural facilitation intervention is a novel manual
physical therapy approach with anecdotal evidence in reducing
peripheral neuropathy symptoms. The main concept of intraneural
facilitation is the use of 2 manual holds. The ﬁrst hold is called
facilitation hold (ﬁg 2) and includes putting the contralateral joint
in a maximal loose-pack position that is comfortable to the pa-
tient. For example, the ankle joint on the contralateral side is
placed in full planter ﬂexion and inversion. This position is sus-
tained during the whole session with a stretch strap. It is important
to note that there is no muscle activity in the joint where the
facilitation is occurring, only a slight stretch. We hypothesize that
with the joint in this position, the nerve will move further than the
artery because the artery has more elastin. With increased neural
excursion in relation to the artery, the nutrient vessels that are
clustered at the joint will be stretched. This stretch may enlarge
the opening at the junction of the artery and bridging nutrient
vessel, therefore consistently creating a vascular bias into the
neural epineurial capillaries. Theoretically, this creates increased
epifascial vascular pressure.
Although anecdotally the effects of
intraneural facilitation were observed in the clinic, the authors are
unaware of other research evaluating the effects of nonextreme
joint positions on nutrient vessel blood ﬂow. Lundborg and
described a relation between pathologic neural
stretching with fascicle deformation and a reduction of blood ﬂow
in the nutrient vessels. The authors found it interesting that a
relation between neural stretching, albeit extreme, and nutrient
vessel blood ﬂow did not exist. However, Lundborg
study how the nonpathologic gentle holds would affect neuro-
vascular blood ﬂow in nutrient vessels.
With increased endoneurial edema and a strong perineurium,
the pressurized blood ﬂow may not push through the
Table 2 Changes in mTNS, SOT, LOS test, and ABC scale (NZ13)
Preintervention, Mean SD Postintervention, Mean SD Mean Difference 95% Conﬁdence Interval P
mTNS 10.624.37 7.774.19 2.85 11.28 to 39.60 .001*
SOT 53.7721.81 6614.32 12.23 0.21 to 2.38 .012
RT 0.910.62 0.810.36 0.10 0.46 to 0.25 .544
DCL 55.4432.57 63.1520.45 7.71 15.38 to 30.80 .834*
EPE 39.6823.61 48.3117.15 8.62 10.03 to 27.28 .334
MVL 1.991.25 3.281.26 1.29 0.21 to 2.38 .023
MXE 54.3131.87 68.4624.14 14.15 11.28 to 39.59 .249
ABC 71.4225.78 78.0217.01 6.60 NA .119
Abbreviations: DCL, directional control; EPE, end point excursion; mTNS, modiﬁed Total Neuropathy Scale; MVL, movement velocity; MXE, maximum
excursion; NA, not applicable; RT, reaction time.
* From Wilcoxon signed-rank test.
From paired ttest.
Fig 2 Facilitation hold includes positioning the contralateral ankle
joint in a maximal loose-pack position of plantar ﬂexion and inver-
sion. This position is maintained throughout the entire session.
4 A. Alshahrani et al
transperineurial vessels that cross the perineurium into the endo-
neurial capillaries. A second hold or mild stretch is necessary to
bias the increased epineurial blood ﬂow past the perineurium into
the endoneurial capillaries. This hold potentially provides an
unweighting pressure. The second hold or stretch will also enable
the therapist to bias circulation in the neural structures that appear
to be most affected. For example a hamstring stretch would bias
blood ﬂow into the sciatic nerve microvasculature (ﬁg 3). Previous
studies demonstrated short-term exercise effects on endoneurial
capillaries, including stimulating endothelial vasodilation,
enhancing endoneurial blood ﬂow, improving abnormal nerve
perfusion, increasing the release of nitric oxide, and enhancing the
concentration of Na/K ATPase.
We hypothesize that improve-
ments in the modiﬁed Total Neuropathy Scale of our subjects were
caused by these immediate vascular changes that occurred in the
treated extremities; however, more research is need to substantiate
Medical records indicating the degree of glycemic control
were not available to researchers for all subjects.
Our study limitations include the potential for bias with the
modiﬁed Total Neuropathy Scale assessment because the clinician
who provided the treatment also assessed the modiﬁed Total
Neuropathy Scale pre- and postintervention. Other limitations
were not having a control or sham group and the small sample size
that does not allow for generalization of our study ﬁndings.
Moreover, this study only measured short-term beneﬁts of the
This pilot study showed that intraneural facilitation improves
static and dynamic balance measures and neuropathy symptoms
using validated measures in patients with diabetic DSPN. Whether
the improvements in balance measures noted in the intervention
subjects translate into decreased fall risk in daily life is uncertain.
However, given the minimal risk associated with intraneural
facilitation, we believe our results warrant further study of this
technique in patients with diabetic and idiopathic DSPN to
establish long-term beneﬁts, measure the effect of intraneural
facilitation on pain measures, and if possible use a control or
a. NeuroCom SMART Balance Master; Natus.
b. SPSS Statistics 22; IBM.
Diabetes mellitus; Diabetic neuropathies; Musculoskeletal
Eric Johnson, DSc, 24951 North Circle Dr, Nichol Hall A-712,
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