Ultrasound in Med. & Biol., Vol. -, No. -, pp.

18, 2016
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http://dx.doi.org/10.1016/j.ultrasmedbio.2016.08.022

d Original Contribution

THE EFFECTIVENESS OF RADIAL EXTRACORPOREAL SHOCK WAVES FOR

TREATMENT OF CARPAL TUNNEL SYNDROME: A RANDOMIZED CLINICAL
TRIAL

GHOLAM REZA RAISSI,* FATEMEH GHAZAEI,* BIJAN FOROGH,* SEYED PEZHMAN MADANI,*
ABBAS DAGHAGHZADEH,y and TANNAZ AHADI*
* Neuromusculoskeletal Research Center, Iran University of Medical Sciences, Tehran, Iran; and y Department of Physical
Medicine and Rehabilitation, Arak University of Medical Sciences,
Arak, Iran

(Received 17 February 2016; revised 11 August 2016; in final form 16 August 2016)

AbstractThis study examined the effectiveness of radial extracorporeal shock wave therapy in the treatment of
carpal tunnel syndrome (CTS). Forty patients with mild to moderate CTS were allocated to two groups: (i) shock
wave 1 wrist splint and (ii) wrist splint. Patients used wrist splints followed by three sessions of low-energy shock
wave therapy in the intervention group and wrist splints alone in the other group. The QuickDASH Questionnaire,
visual analogue scale and nerve conduction studies were used to evaluate the patients before the study and at 3, 8
and 12 wk after the start of the treatment. At the end of the study, both groups saw the same clinical benefits. How-
ever, a significantly greater improvement in the median nerve distal sensory latency was noted in the shock wave
group compared with the control group. We suggest that application of shock wave with alternative protocols may
be effective in the treatment of CTS in future studies. (E-mail: tannaz.ahadi@yahoo.com) 2016 World Feder-
ation for Ultrasound in Medicine & Biology.
Key Words: Carpal tunnel syndrome, Splint, Median neuropathy.

INTRODUCTION A newly emerging, non-invasive therapeutic method

in the treatment of CTS is extracorporeal shock wave
Carpal tunnel syndrome (CTS), caused by compression
(ESW) therapy. Over the last 10 y, ESW therapy has
of the median nerve in the carpal tunnel, is the most com-
become a common and successful method in the treat-
mon peripheral entrapment neuropathy (Papanicolaou
ment of various inflammatory musculoskeletal disorders,
et al. 2001).
such as plantar fasciitis and lateral epicondylitis and so on
The classic symptoms of CTS include numbness,
(Romeo et al. 2014; Wang 2003; Wang and Chen 2002;
tingling and pain of the three radial digits, which can
Wang et al. 2002a, 2002b; Rompe et al. 2001).
progress to permanent sensory and/or motor loss in the
The potential benefits of ESW therapy in the man-
later stages (Walter et al. 2008). Although there are
agement of peripheral neuropathies have recently
many conservative methods of management, such as a
received greater attention. Shock waves promote axonal
wrist splint, steroid injections and laser therapy, their
regeneration of peripheral nerves through several molec-
effectiveness is minimal (OConnor et al. 2003).
ular reactions (Hausner and Nogradi 2013; Hausner et al.
Wrist splints traditionally have been used as one of
2012; Lee and Cho 2013). Recently, radial shock waves
the most common treatments for CTS with a reported suc-
demonstrated their effectiveness in neuropathic pain of
cess rate of 31%67%, if applied during early stages of
rats with chronic constriction injuries (Fu et al. 2014).
the disorder (Premoselli et al. 2006).
Radial extracorporeal shock waves (RESWs) differ
from focused extracorporeal shock waves (FESWs).
Focused shock waves require accurate identification of
the targeted area while the radial waves disperse eccentri-
Address correspondence to: Tannaz Ahadi, Neuromusculoskele- cally from the applicator tip without focusing at a targeted
tal Research Center, Department of Physical Medicine and Rehabilita-
tion, Firoozgar Hospital, Iran University of Medical Sciences, Valiasr
spot. The energy produced by RESWs is highest at the
Square, Beh Afarin St., Tehran, Iran. E-mail: tannaz.ahadi@yahoo.com skin surface, diverging and weakening as it penetrates

1
2 Ultrasound in Medicine and Biology
deeper (Romeo et al. 2014). A recent systematic review
reported that some advantages of RESW therapy over
traditional FESW therapy include a larger treatment
area, no need for exact localizing the target area, no
requirement for local anesthesia and low cost (Chang
et al. 2012).
In recent years, few studies have reported the use of
shock wave therapy as an alternative management for
treating CTS (Notarnicola et al. 2015; Paoloni et al.
2015; Seok and Kim 2013).
Seok and Kim (2013) compared the efficacy of ESW
therapy with local steroid injection in the treatment of
CTS. According to the results of this study, shock waves
may be as effective as local steroid injection in relieving
the symptoms.
Paoloni et al. (2015) compared the short-term effi-
cacy of ultrasound (US) therapy and ESW therapy on
mild and moderate CTS and found the patients in the
ESW group showed greater pain improvement at a 12-
wk follow-up compared with both the US and cryo-US
groups. Notarnicola et al. (2015) examined the efficiency
of shock wave therapy versus dietary supplements in
managing CTS and reported that both treatments are
effective in controlling of the symptoms and improving
the evolution of CTS. Another clinical trial evaluated
the effect of ESW on CTS surgical complications (pillar
syndrome), reporting pain regression and improvement
of surgical scarring (Romeo et al. 2011).
However, the above studies used focused shock
waves, and none has entirely proven the effects of ESW
therapy on CTS. Recently, Wu et al. (2016) evaluated
the effect of radial shock waves on CTS patients and
demonstrated that RESW therapy is an effective method
for relieving pain and disability in patients with CTS.
ESW therapy is a potentially novel approach for treating
CTS. While a few papers have reported the effects of
ESW therapy on CTS, no treatment protocol for RESW
therapy has been established. Several questions,
including the most effective and safe intensity of ESW
therapy, remain unanswered, and further studies need to
be conducted to resolve these queries and to confirm
the results of the previous studies. Because of the poten-
tial risk of nerve damage and intolerance of a high-energy
protocol (used in the Wu et al. study) by our patients, we
decided to try a low-dose, painless protocol.
We conducted a prospective randomized, controlled
study to assess the effect of low-dose painless RESW
therapy protocol for treating CTS.
MATERIALS AND METHODS
Participants
Forty patients aged between 18 to 70 y with mild and
moderate CTS were recruited during a randomized, sin-
Volume -, Number -, 2016
gle blinded, controlled clinical trial method. Participants
were visited in the physical medicine and rehabilitation
clinic at Firoozgar Hospital. Inclusion criteria were
typical signs and symptoms of CTS, including pares-
thesia, numbness or pain in the median nerve distribution
for more than 1 mo, visual analogue scale (VAS) $4, pos-
itive Tinels sign or Phalens test in physical examination
and confirmed diagnosis of mild to moderate CTS with
electrophysiological study. A positive Tinels sign is
described as a tingling sensation in the nerve anatomic
distribution, which occurs as a result of light percussion
over a nerve. Phalens test is described as positive when
full flexion of the wrist for 60 s causes paresthesia in
the territory of the median nerve (Urbano 2000).
Pregnant women and patients with severe CTS, pre-
vious carpal tunnel release surgery, corticosteroid injec-
tion in carpal tunnel within the last 3 mo and a history
of wrist fractures were excluded. In addition, people
with abnormal electrophysiological findings other than
CTS, such as cervical radiculopathy or peripheral neurop-
athy, were also excluded.
Ethical consideration
All participants enrolled in this study were well
informed regarding the methods, aims and possible side
effects of treatments. This study was approved by the
Ethics Committee and was registered at the Registry of
Clinical Trials (IRCT2014083118991 N1). After written
informed consent was obtained, patients were random-
ized into two groups: (i) RESW therapy 1 wrist splint
and (ii) wrist splint. We used a block randomization
method with a 1:1 ratio according to severity of disease
(mild or moderate CTS).
Procedures
After pre-treatment evaluations and to provide
fundamental treatment for CTS, a night wrist splint was
prescribed for each patient in both groups. A Neoprene
wrist splint with metal bar support was firmly fixed on
the wrist in 05 extension. Patients were advised to
avoid repetitive flexion and extension of the wrist. In
cases of bilateral CTS to comply with ethical codes, the
wrist splint was prescribed for both hands. However,
only the hand with more severe symptoms was evaluated.
In the intervention group, participants underwent
three RESW therapy sessions once per wk for 3 consec-
utive wk. The shock wave probe was placed perpendicu-
larly on the patients palm over the median nerve on the
carpal tunnel after application of the coupling gel. The
median nerve was localized by anatomic landmarks on
the wrist (between the flexor carpi radialis and palmaris
longus tendons). Due to pain and intolerance of a high-
energy protocol by our patients, we used a painless,
low-dose protocol as a pilot in a few patients. This
 Extracorporeal shock waves for treatment of carpal tunnel syndrome d G. R. RAISSI et al.
protocol was then chosen because of patient tolerance.
Shock waves were administrated without anesthesia us-
ing a pneumatic generator (BTL 6000 SWT Topline,
2010, Hertfordshire, UK) with 1000 shocks at a pressure
of 1.5 Bar and a rate of 6 pulses per s. All patients were
asked to avoid any other treatments, such as local steroid
injection, non-steroidal anti-inflammatory drugs and
laser therapy for the extent of the study (for 12 wk after
the first treatment session).
Outcome measures
All measurements were performed at baseline and
the follow-ups by the same physician, who was unaware
of the grouping. In both groups, evaluations were per-
formed before treatment and at 3, 8 and 12 wk after the
start of the treatment (after the first session of shock
wave therapy in the interventional group).
Primary outcome. The VAS was used to quantify
pain and tingling within the last wk. The patients made
a mark on a 10-cm horizontal line. Zero represents no
pain and 10 represents maximum pain or unbearable pain.
Secondary outcomes: Quick Disabilities of the
Arm, Shoulder, and Hand Questionnaire (Quick
DASH). QuickDASH is a standardized questionnaire
that evaluates impairments and activity limitations in
patients with upper extremity disorders (Jester et al.
2005).
The symptoms and functional status were evaluated
with standard QuickDASH. This Questionnaire has been
validated for our patients (Mousavi et al. 2008). It con-
sists of 11 questions to assess the severity, frequency
and duration of symptoms and the amount of disturbance
during daily activities. Each item is scored between 1 and
5 (5 is equivalent to the more severe symptoms). The final
score ranges from 0 (no disability) to 100 (maximum
disability) (Gummesson et al. 2006).
Median nerve conduction studies. Electrodiagnostic
evaluation was performed by a Schwarzer
topas electrophysiological examination unit with two
channels (Natus, Bavaria, Germany). Before the examina-
tion, skin temperature was measured. If the temperature
was below 32 C, hands were warmed with a hot pack for
10 min. Before commencing the treatment, all patients
were evaluated for other conditions, such as cervical radi-
culopathy, brachial plexopathy and other impingements of
the median nerve or peripheral neuropathies that could
produce similar symptoms to CTS.
In the electrophysiological examinations, median
sensory and motor distal latencies and amplitudes were
evaluated. Sensorimotor response measurements were
performed according to the standard protocol (Dumitru
et al. 2002). Median sensory nerve action potential
3
(SNAP) was performed anti-dromically, through supra-
maximal stimulation of median nerve on the wrist be-
tween the flexor carpi radialis and palmaris longus tendon
at a distance of 14 cm from the active recording electrode
(the active and reference recording electrodes were fixed
on the third finger with distance of 4 cm). The time it
takes for electrical impulse to travel from the stimulation
to the recording site is called latency and is measured in
ms. The maximal normal range of sensory peak latency
is 3.6 ms and the minimum normal limit of amplitude
on base-to-peak measurements is 10 mv.
Median compound motor action potential (CMAP)
was performed through supra-maximal stimulation of the
median nerve at the wrist with a distance of 8 cm from
the active recording electrode and recording of response
with bar pad from the thenar eminence. Maximum normal
limit of the median motor onset latency is 4.2 ms and min-
imum amplitude of peak-to-peak measurement is 5 mv. Pa-
tients with a sensory distal latency of longer than 3.6 ms
with normal motor latency (mild CTS) and prolonged mo-
tor distal latency (moderate CTS) were enrolled in the
study (Dumitru et al. 2002).
Statistical analysis
For the statistical analysis, SPSS for Windows
version 22 was used. The c2 test and independent t-test
were used for analysis of demographic data and baseline
evaluations. The paired t-test was used to determine the
changes from baseline to 3, 8 and 12 wk after treatment
for each group. The outcomes at each follow-up visit
were compared with the baseline. Analysis of differences
between the two study groups was performed using the
independent t-test, and p # 0.05 was considered statisti-
cally significant.
RESULTS
Initially, 115 patients with CTS were screened for
eligibility; of them, 70 were excluded based on exclusion
criteria and five patients decided to leave the study. Thus,
a total of 40 patients (20 in each group) were enrolled and
were block randomized into interventional and control
groups. During follow-up, five patients (two patients in
the interventional group and three patients in the control
group) dropped out because of traveling, so they were re-
placed with patients who met the inclusion criteria.
Finally, the results were obtained from 40 patients who
completed the study (Fig. 1).
The baseline demographic and clinical characteris-
tics are summarized in Table 1. There was no statistically
significant difference between the two groups in demo-
graphic characteristics including age, gender, BMI and
duration of symptoms. No statistically significant differ-
ence was found between the groups in terms of
4 Ultrasound in Medicine and Biology Volume -, Number -, 2016

Enrollment

Assessed for eligibility (n=115 )

Excluded (n= 75 )
Not meeting inclusion criteria (n= 70 )
Declined to participate (n=5 )

Randomized (n= 40 )

Allocation
Allocated to intervention (n=20) Allocated to control (n=20)
Received 3 sessions of radial shock wave Received only wrist splint
+ wrist splint

Follow-Up
Lost to follow-up (give reasons) (n=2) Lost to follow-up (give reasons) (n= 3)

Were replaced by patients who met the Were replaced by patients who met the
inclusion criteria inclusion criteria

Analysis
Analysed (n= 20) Analysed (n=20)

Fig. 1. Flow of participants through the study.

pre-treatment values of VAS, QuickDASH score or elec-
trophysiological parameters (p . 0.05; Table 1).
There was a significant improvement in post-
treatment values of VAS, QuickDASH score, SNAP distal
latency and CMAP distal latency in both groups
(Table 2).
A comparison of the two groups indicated a statisti-
cally significant decrease in the post-treatment values of
SNAP distal latency in the interventional group at 3 wk,
8 wk and 12 wk after treatment. Although a greater
improvement in VAS and the QuickDASH score was
noted in the intervention group compared with that in
the control group, the differences were not significant
(Table 3). The results of our study were somewhat
different from Wu et al. (2016) study. In their study,
greater improvement in the subjective scores, such as
the VAS and Boston Carpal Tunnel Questionnaire
(BCTQ) was noted in the intervention group compared
with the control group. However, they did not observe a
significant increase in sensory nerve conduction velocity
after an additional three RESW therapy sessions
compared with splinting alone. No serious side effect
was found in any of the patients, except one patient
who complained of transient wrist pain after 12 wk.
DISCUSSION
This study is the second prospective randomized,
controlled trial to investigate the effect of RESW therapy
for treating CTS. In this study, 40 patients with mild and
moderate CTS were divided into a shock wave interven-
tional group and a control group. Both groups saw the
same clinical benefits. However, a significantly greater
improvement in the distal sensory latency of the median
nerve was noted in the shock wave group compared
with the control group.
CTS is caused predominantly by compression of
the median nerve at the wrist because of the swelling
of the flexor synovium. Pain is thought to be secondary
to nerve ischemia rather than direct physical damage
 Extracorporeal shock waves for treatment of carpal tunnel syndrome d G. R. RAISSI et al. 5

Table 1. Demographic and baseline characteristics of the multiple studies to have anti-inflammatory effects in
groups musculoskeletal disorders. According to some animal
RESW studies, the main mechanism of action of ESW therapy
therapy Control in the musculoskeletal disorders is primary excitation of
Characteristics (n 5 20) (n 5 20) p value growth factors, including endothelial nitric oxide syn-
Age thase, vascular endothelial growth factor and prolifer-
y 46.1 (1.95) 46.65 (2.23) 0.854 ating cell antinuclear antigen. Production of nitric oxide
Gender, n (%) induced by ESW therapy plays a major role in increasing
Male 2 (10) 1 (5) 0.854
Female 18 (90) 19 (95) the level of angiogenetic growth factors and inhibition of
Body mass index, n (%) inflammation through the suppressed production of pro-
kg/m2 29.8 (1.15) 31.05 (1.24) 0.472
Symptom duration, n (%)
inflammatory cytokines (Romeo et al. 2014).
$3 mo 18 (90) 18 (90) 1 In our study, improvement of the median sensory
#3 mo 2 (10) 2 (10) distal latency in the interventional group may be due to
Lesion site, n (%)
Left 5 (25) 6 (30) 0.484
the improvement of localized inflammation within the car-
Right 1 (5) 3 (15) pal tunnel. On the other hand, several recent studies have
Bilateral 14 (70) 11 (55) suggested potential benefits of shock waves on re-
Dominant hand lesion, n (%)
Dominant 10 (50) 15 (75) 0.095
innervation. Hausner et al. (2012) reported that low-
Recessive 10 (50) 5 (25) energy shock waves could induce significant recovery of
Visual analogue scale nerve regeneration, nerve conduction velocity and ampli-
Mean (SD) 6.1 (0.38) 5.95 (0.42) 0.795
QuickDASH tude in rats treated with autografts of the sciatic nerve. The
Mean (SD) 45.6 (3.77) 54.5 (4.44) 0.134 regrowth of axons is supported by the rapid proliferation
NCS parameters of Schwann cells in the distal stump providing a contact
SNAP distal latency 4.34 (0.09) 4.59 (0.17) 0.210
(mean 6 SD) guide for them. ESW therapy induces Schwann cell prolif-
CMAP distal latency 4.69 (0.18) 4.54 (0.16) 0.519 eration, accelerated removal of damaged axons, increased
(mean 6 SD) myelin synthesis and axonal regeneration (Hausner and
SNAP amplitude 17.68 (1.99) 20.36 (2.13) 0.365
(mean 6 SD) Nogradi 2013; Hausner et al. 2012; Lee and Cho 2013).
CMAP amplitude 11.76 (0.88) 12.84 (0.57) 0.308 It appears that improved vascularization, the main
(mean 6 SD) mechanism of shock wave effect in the musculoskeletal
CMAP 5 compound muscle action potential; NCS 5 nerve conduc- disorders, does not have a direct role in improving nerve
tion study; QuickDASH 5 Disabilities of the Arm, Shoulder and Hand; regeneration (Hausner et al. 2012).
RESW 5 radial extracorporeal shock wave; SNAP 5 sensory nerve ac- To date, there are few clinical trials dealing with the
tion potential.
effect of shock waves in the treatment of CTS. Seok and
Kim (2013) compared shock wave efficacy with local ste-
of the nerve. The damaged median nerve within the roid injection in patients with CTS. In both groups, signif-
carpal tunnel, initially undergoing demyelination fol- icant improvement was observed in the VAS and the
lowed by axonal degeneration. Sensory fibers often symptom severity score. There was not a significant dif-
are affected first, followed by motor fibers (Kerwin ference in VAS and symptom severity score between
et al. 1996). the two groups. However, significant improvement in
The improvement of the distal sensory latency in the the median sensory distal latency was only seen in the in-
shock wave group implies that RESW therapy may have jection group compared with the shock wave group. In
an effect on myelin synthesis (the main primary pathol- contrast to the Seok and Kim study, the median sensory
ogy in CTS) rather than axonal regeneration. latency was significantly improved in the shock wave
On the other hand, the electrophysiological studies group compared with the control group in our study.
only reveal the involvement of the large myelinated nerves The significant improvement in the objective median sen-
while the symptoms of CTS are mainly related to the small sory latency is more important than subjective scores,
non-myelinated sensory nerve involvement. Small nerve such as VAS. In the Seok and Kim study, relatively
fibers cannot be assessed in routine nerve conduction high-energy focused shock waves (energy flux density
studies (Gursoy et al. 2013). This is why we saw improve- of up to 0.29 mJ/mm2) were used, while we applied
ment of nerve conduction in the study, with no meaningful low-energy radial shock waves, which have some advan-
improvement of the patients symptoms. In other words, tages, including no need for exact localization of the
there is no true correlation between the symptoms of pa- target area and higher availability.
tients and nerve conduction study parameters. In their study, the interventional group received one
A new treatment under investigation for the manage- session of ESW therapy. In our study, despite the three
ment of CTS is ESW therapy, which has been shown in shock wave sessions, no statistically significant
6 Ultrasound in Medicine and Biology Volume -, Number -, 2016

Table 2. Comparison of pre-treatment and post-treatment values of outcome variables in each group
RESW therapy (n 5 20) Control (n 5 20)

Outcome variables Follow-up sessions Mean 6 SD Paired t-test p* Mean 6 SD Paired t-test p*

Baseline 45.6 6 3.77 54.53 6 4.44

QuickDASH 3 wk 28.53 6 3.60 0.001. p 70.35 6 32.08 0.621
8 wk 21.80 6 3.21 0.001. p 31.1 6 3.84 0.001. p
12 wk 22.17 6 3.80 0.001. p 29.68 6 4.04 0.001. p
Baseline 4.34 6 0.09 4.59 6 0.17
SNAP distal latency 3 wk 4.38 6 0.16 0.004 4.19 6 0.07 0.001
8 wk 4.26 6 0.14 0.003 4.12 6 0.07 0.001. p
12 wk 4.02 6 0.07 0.001. p 4.19 6 0.15 0.001
Baseline 17.68 6 1.99 20.36 6 2.13
SNAP amplitude 3 wk 17.86 6 2.15 0.909 19.11 6 2.01 0.125
8 wk 17.57 6 2.28 0.994 20.71 6 2.01 0.695
12 wk 18.73 6 2.57 1 20.56 6 1.82 0.865
Baseline 4.69 6 0.18 4.54 6 0.16
CMAP distal latency 3 wk 4.49 6 0.16 0.010 4.30 6 0.10 0.010
8 wk 4.44 6 0.16 0.001. p 4.21 6 0.10 0.001
12 wk 4.41 6 0.16 0.001 4.18 6 0.09 0.002
Baseline 11.76 6 0.88 12.84 6 0.57
CMAP amplitude 3 wk 11.78 6 0.68 0.970 12.41 6 0.62 0.266
8 wk 11.95 6 0.64 0.710 12.29 6 0.64 0.181
12 wk 11.78 6 0.61 0.974 11.65 6 0.59 0.008
Baseline 6.1 6 0.38 5.95 6 0.42
Visual analogue scale 3 wk 4 6 0.52 0.001. p 4.15 6 0.47 0.001. p
8 wk 3.25 6 0.56 0.001. p 3.35 6 0.42 0.001. p
12 wk 2.85 6 0.57 0.001. p 3.30 6 0.42 0.001. p

CMAP 5 compound muscle action potential; QuickDASH 5 Disabilities of the Arm, Shoulder and Hand; RESW 5 radial extracorporeal shock
wave; SNAP 5 sensory nerve action potential.
* Compared with baseline.

differences were observed in the clinical and functional
parameters between the two groups, except for median
nerve sensory latency. This could be partly explained
by a more sensitive outcome measure (i.e., Boston CTS
Questionnaire) in their study. The Boston Questionnaire
comprises two scales, a symptom severity scale (SSS)
and a functional status scale (FSS) in patients with
CTS. The SSS indicates how bad the symptoms feel to
the patient and the FSS indicates how much interference
the symptoms cause with activities of daily living. The
SSS has 11 questions scored from 1 point (mildest) to 5
points (most severe). The FSS has 8 questions scored
from 1 point (no difficulty with activity) to 5 points
(cannot perform the activity at all). The overall score
for both scales was calculated as the mean of the items.
We used the standard and validated QuickDASH Ques-
tionnaire because there was not the validated version of
Boston CTS Questionnaire (BCTQ) in our country at
the time of this study. The QuickDASH consists of 11
questions to measure physical function and symptoms.
Each item is scored between 1 and 5 (5 is equivalent to
the more severe symptoms). The final score is from
0 (no disability) to 100 (maximum disability). This Ques-
tionnaire mainly measures the functional status of the
hand and does not assess the severity of hand symptoms.
The functional status score reflects the functional status,
which needs more time for meaningful changes.
Several studies have shown a dose-dependent effect
of shock wave over time. Multiple shock wave sessions
may lead to improvement of other parameters, including
axonal regeneration and longer lasting effects. Shock
wave application can induce small nerve fiber degenera-
tion. Given that small fibers transmit pain signals, this
could cause a short-term pain relief through desensitiza-
tion. Re-innervation occurs slower in multiple shock ses-
sions. These data show that a second application has
longer lasting effects than single session (Takahashi
et al. 2006).
Recently, Wu et al. (2016) published a study similar
to our trial. They evaluated the effect of radial shock
waves on CTS patients. Participants in the intervention
group underwent three sessions of RESW therapy with
nightly splinting, whereas those in the control group un-
derwent sham RESW therapy with nightly splinting.
They demonstrated that significantly greater improve-
ment in the VAS and Boston CTS Questionnaire scores
was noted in the intervention group. However, they did
not observe a significant increase in sensory nerve con-
duction velocity after an additional three RESW therapy
sessions compared with splinting alone. The distance be-
tween the stimulating and receiving electrodes is divided
by the impulse latency, resulting in nerve conduction ve-
locity. In our study, patients with mild and moderate CTS
were evaluated. It is surprising that in the Wu et al. study
 Extracorporeal shock waves for treatment of carpal tunnel syndrome d G. R. RAISSI et al. 7

Table 3. Changes in the outcome variables from baseline high-energy ESW therapy on unmyelinated and myelin-
to 3 wk, 8 wk and 12 wk after treatment in the ated fibers, there is a growth-promoting effect of
intervention group compared with the control group
low-energy ESW therapy on myelinated fibers and subse-
RESW therapy quently the long-term effects.
(n 5 20) Control (n 5 20) High-energy shock waves induce injury of the small
Difference Follow-up Mean 6 SD Mean 6 SD p* nerve fibers within the exposed area. Given that small fi-
bers transmit pain signals, this could cause a short-term
QuickDASH 3 wk 217.08 6 3.21 15.8 6 31.44 0.305 pain relief through desensitization but not eliminate the
8 wk 223.8 6 4.2 223 6 3.2 0.883
12 wk 223.4 6 4.59 224.8 6 4.38 0.825 basic cause of pain. Over time, subsequent active axonal
SNAP distal 3 wk 20.2 6 0.06 20.15 6 0.04 0.050 regeneration may account for the re-innervation of the
latency 8 wk 20.33 6 0.09 20.22 6 0.045 0.005 exposed area and the amelioration of the desensitization
12 wk 20.4 6 0.1 20.33 6 0.59 0.012
SNAP 3 wk 0.17 6 1.51 21.25 6 0.77 0.409 (Murata et al. 2006). This finding suggests that the
amplitude 8 wk 20.11 6 1.54 0.35 6 0.89 0.796 improvement of symptoms in Seok and Kim and Wu
12 wk 1.04 6 1.62 0.2 6 1.16 0.674 et al. studies could be related to the use of high-energy
CMAP distal 3 wk 20.2 6 0.07 20.23 6 0.08 0.817
latency 8 wk 20.25 6 0.06 20.32 6 0.08 0.509 ESW therapy and subsequent desensitization through
12 wk 20.28 6 0.07 20.36 6 0.09 0.555 the small fiber damage. While we used low-energy
CMAP 3 wk 0.015 6 0.38 20.43 6 0.37 0.412 RESW therapy and subsequently its growth-promoting
amplitude 8 wk 0.19 6 0.5 20.55 6 0.39 0.254
12 wk 0.02 6 0.61 21.19 6 0.405 0.108 effect on myelinated fibers may have resulted in improve-
Visual 3 wk 22.1 6 0.33 21.8 6 0.18 0.435 ment of sensory latency.
analogue 8 wk 22.85 6 0.46 22.6 6 0.21 0.624
scale 12 wk 3.2 6 0.48 22.65 6 0.25 0.281
To date, no published neurologic complications
from low-energy ESW therapy have been reported in
CMAP 5 compound muscle action potential; the literature. The most reported adverse events are tran-
QuickDASH 5 Disabilities of the Arm, Shoulder and Hand;
RESW 5 radial extracorporeal shock wave; SNAP 5 sensory nerve ac-
sient pain and redness of the skin as well as small hema-
tion potential. toma, which usually resolve spontaneously (Wild et al.
* Compared between groups. 2000).
Several limitations must be acknowledged. First, the
majority of the participants were female. Hence, this data
the severity of CTS is not mentioned, so they might have cannot be generalized to the male population. Second, the
evaluated only patients with mild CTS. control group and radial shock wave group had no signif-
In contrast to the Wu et al. study, the median sensory icant difference in clinical outcomes in contrast to the
latency was significantly improved in the shock wave Seok and Kim and Wu et al. studies. They used a more
group compared with the control group in our study. In sensitive outcome measure (BCTQ vs DASH), and so
their study, the RESW therapy was administered with the choice of a noncondition-specific clinical outcome
2000 shots, at a pressure of 4 Bar and a frequency of measure is a weakness of our study as well. Third, the
5 Hz. We used 1000 low-energy shots, at a lower pressure routine nerve conduction study can only evaluate large
(1.5 Bar) and a frequency of 6 Hz. Some animal studies diameter fibers and not small fiber involvement, so we
have shown that high-energy ESW therapy can result in did not assess small nerve fibers. Fourth, it would be bet-
histologic damage to the myelin sheath of myelinated fi- ter to have sham ESW therapy in the control group. How-
bers and induce substantial loss of small unmyelinated ever, this does not seem to interfere with the results of our
nerve fibers (Bolt et al. 2004; Hausdorf et al. 2008; study because no meaningful difference was found in the
Mense and Hoheisel 2013; Ohtori et al. 2001; Wang intervention group compared with control group in terms
et al. 2002a, 2002b). A large body of evidence suggests of clinical symptoms. Finally, the most effective intensity
that shock wave doses greater than 900 impulses and the appropriate number of ESW therapy shots and
combined with a flux density of 0.08 mJ/mm2 can sessions remain unclear, and further studies are needed
induce damage to the affected nerves, manifested in with a larger number of patients with alternative protocols
impaired electrophysiological parameters and (such as the use of more sessions, different shock inten-
degeneration of the myelin sheaths at the levels of light sity or combined ESW therapy with other therapeutic mo-
and electron microscope (Bolt et al. 2004). It is thought dalities) to resolve these queries.
that RESW therapy at a lower pressure (1 bar) may
have better application prospects in compression neurop-
CONCLUSIONS
athy, according to the principle of the minimum effective
dose (Fu et al. 2014). This study is the second clinical trial using radial
The level of energy flux density appears to be crucial shock wave therapy in patients with CTS. The results re-
for the efficacy. In contrast to the deleterious effects of vealed that despite there being no significant difference in
8 Ultrasound in Medicine and Biology
improvement of the symptoms with three sessions of
shock wave therapy compared with the control group, it
lead to an improvement in median sensory latency. Ac-
cording to the findings of our study, low-energy shock
waves may represent an effective and non-invasive treat-
ment in cases of nerve compression where fiber regener-
ation is necessary.
Since the efficacy of RESW therapy seems to be
dose dependent, application of shock wave with alterna-
tive protocols, such as the use of more sessions and the
use of different shock intensity or frequency with longer
follow-up time may be more conclusive in future studies.
Future studies to explore best parameters for opti-
mizing the efficacy of RESW therapy are needed.
AcknowledgmentsThe authors thank Ashkan khakpur Saebi, MD, for
comments that improved the manuscript.
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