DOTTORATO DI RICERCA IN MEDICINA FISICA E RIABILITATIVA
SPERIMENTALE DELL’APPARATO LOCOMOTORE
XXIV CICLO
ULTRASOUND-GUIDES ASPIRATION AND CORTICOSTEROID INJECTION
COMPARED TO HORIZONTAL THERAPY FOR TREATMENT OF KNEE
OSTEOARTHRITIS COMPLICATED WITH BAKER’S CYSTI: A RANDOMIZED,
SINGLE BLIND, CONTROLLED TRIAL.
Candidato
Relatore
Dott. Alessandro Cerino
Prof. Valter Santilli
Anno Accademico 2010-2011
Introduction
BC is a fluid distension of a bursa between the gastrocnemius and
semimembranosus tendons that fills an anatomical communication
with the knee joint1. It can be classified anatomically and
clinically as a primary or, more frequently, as a secondary cyst.
Several authors have reported that 41% to 83% of joint disorders
have associated popliteal secondary cysts2. Meniscal tears, and
degenerative joint disease, infectious arthritis, polyarthritis,
villonodular synovitis and some connective tissue diseases are
pathologies commonly associated with BC3. Therapy for BC
depends on the primary cause, but intra-articular corticosteroid
injection or a direct puncture of the cyst for aspiration and
corticosteroid administration are widespread practices.4,5,6
Physical therapy agents, e.g. transcutaneous electrical nerve
stimulation (TENS), interferential therapy (IFT) or percutaneous
electrical nerve stimulation, play an important role in the treatment
of
knee
OA7,8.
Deep
heat
such
2
as
short
waves
and
electrotherapeutic modalities such as interferential therapy (IFT)
are used for the treatment of acute and chronic pain, which are the
cardinal symptoms of OA9,10. Horizontal therapy (HT) is a novel
analgesic therapy that is expected to extend the advantages of
traditional IFT. HT envisions that the intensity of the electricity is
constant, whereas the frequency of the electric impulse is modified
during application. HT has been found to be effective in treating
lower back pain in patients suffering from osteoporosis11.
No studies exist concerning the effectiveness of electrical nerve
stimulation in patients having knee OA complicated with BC. To
the best of our knowledge, electrical therapies play a role in pain
relief and improvement of function. Nevertheless, little known
about the possibilities of using physical therapies in complicated
knee OA. Furthermore, combining different therapies, i.e.
pharmacological and physical therapies, generally produces better
outcomes for symptoms of knee OA than do isolated therapies12.
We therefore propose that better outcomes may be obtained also in
3
knee OA complicated by BC, when a multi-model therapeutic
approach rather than a single therapy is applied. We designed a
RCO in order to assess if HT and aspiration alone or in
combination determine pain relief and functional improvement in
a group of patients with knee OA complicated by BC.
Methods
Consecutive patients of both sexes attending our outpatient clinic
between June 2009 and September 2010 with a knee OA and a
clinical suspicion of BC were initially enrolled in the study.
Clinical and radiographic criteria of the American College of
Rheumatology for knee OA13 were used to detect knee OA. To be
included, diagnosis of BC should be confirmed by means of
standard US evaluation and BC should be symptomatic, i.e.
patients have to refer pain in the posterior aspect of the knee at
rest or during activity and when physical examination showed
painful swelling at palpation of the posterior aspect of the knee
4
and/or tension in the popliteal fossa limiting flexion-extension to a
variable degree.
Patients were excluded if they presented one of the following: a
score K III of Kellgren and Lawrence grading scale13, knee joint
instability; previous open or arthroscopic knee surgery; history of
systemic or local infectious, neoplastic and/or rheumatic diseases
and subject with pace-maker. The procedure followed was in
accordance with the ethical standards of our institution.
Study design
The trial was conducted as a single blind, randomized, controlled
trial. After obtaining written informed consent from all the
subjects, a clinical and instrumental evaluation was performed at
the baseline (T0) to evaluate inclusion and exclusion criteria.
Patients who satisfied the inclusion criteria were randomized to
either the US-guided BC aspiration and corticosteroid injection
group (Group A), the Horizontal Therapy group (Group B) or the
5
US-guided BC aspiration and corticosteroid injection plus
Horizontal therapy group (Group C) using a computer-generated
1:1:1 allocation sequence. All patients in the three groups
underwent clinical and US evaluation at baseline, at the end of the
treatment (T1) and at 1-month follow-up (T2) (figure 1 Flowchart). As a primary outcome measure we considered pain
reduction as measured by visual analog scale (VAS) and by
Western Ontario and McMaster Universities (WOMAC) pain
subscale. As secondary outcome measures we considered
functional improvement, as measured by WOMAC joint stiffness
and disability subscales and reduction of maximal axial and
sagittal areas of the BC, as assessed by means of US. Any adverse
event was also registered during the follow-up period.
US Evaluation
US evaluation was performed in all patients at each follow-up by
the same experienced physician, using a 7.5-MHz linear-array
transducer (GE Healthcare, Logiq P5 pro, Japan). Both sagittal
6
and transverse scans of the popliteal fossa were performed, and
the maximal area of the BC in both directions was calculated
using the built-in software.
Clinical Evaluation
A 10-cm VAS with 0 cm labeled “no pain” and 10 cm labeled “the
worst pain I have ever had” was used to assess pain.
The patient placed a mark somewhere along a line in response to
the question, “With respect to the worst pain you have
experienced in your life, what has been the relative level of your
knee pain in the last 24 hours?” The Italian version of the
WOMAC OA index15, a self-assessment multi-dimensional
instrument that evaluates 17 functional activities, 5 pain-related
activities, and 2 joint stiffness categories in three different
subscales, was used to measure dysfunction and pain.
US-guided BC aspiration and corticosteroid injection.
US-guided aspiration and corticosteroid injection into the BC were
performed by means of a free-hand technique.11
7
With the patient lying prone, a scan of the popliteal region was
obtained. The BC was localized and then, under aseptic
conditions, all patients received an injection through a posteriormedial approach at the level of the joint line, by means of a 22
gauge needle with drawing of serous fluid, until the cyst was
completely decompressed, followed by injection of 40 mg
methylprednisolone acetate and lidocaine hydrochloride.
Horizontal Therapy
Horizontal therapy was delivered through a specific commercial
device (PRO ElecDT 2000, Hako med; D). As regards the location
of the electrical pads, we strictly followed the instructions
provided by the manufacturers of the instruments. Therapy
consisted of the placement of 4 cutaneous electrodal pads (8×13
cm), one in center of the popliteal, one on the patella and two
others at the posterior proximal site of the thighs, with a
stimulation frequency oscillating at 100 Hz between 4400 and
12346 Hz for 30 minutes. Each patient underwent 10 treatments (5
8
per week), each lasting 30 minutes. The first 10 minutes of
treatment consisted of a progressive increase in frequency
according to a logarithmic scale and a subsequent decrease with
frequencies between 4357 and 12346 Hz (DISCAN); the
following 10 minutes of treatment consisted in gradual increase in
frequencies and subsequent decrease between 1 and 100 Hz; the
last 10 minutes of treatment consisted in a fixed frequency to 4357
Hz. In patients of Group C, a complete cycle of HT was started
three days after US-guided aspiration and corticosteroid injection
into the BC.
Sample Size
Based on the results of a previous study
5, 16
the target sample size
of 60 (20 in each group) was calculated to ensure at least 90%
power to detect a difference of 1.7 points with 1.3 points of
standard deviation in change of VAS scores between the treatment
groups using two-side O=0.01, and anticipating that protocol
violators and early discontinuations would amount to 20%.
9
Statistical Analysis
Statistical analyses were carried out using the SPSS version 18
package (SPSS Inc, Chicago, Ill). All primary and secondary
outcome analyses were performed according to the principle of
intention-to-treat. The one-way analysis of variance (ANOVA) or
the Kruskal-Wallis test were used, as appropriate, to detect
differences among groups as regards baseline demographic and
clinical characteristics. The choice of parametric or nonparametric
tests was dictated by the results of a normality test. A 2-way
ANOVA with group as the between-subjects factor and time as the
within-subjects factor was used to detect any significant
differences between the three groups and within each group before
and after treatment and at 1-month follow-up. A Tukey post hoc
comparison was used to detect any significant differences between
the mean values when a significant main effect and interaction
were found. The level of significance was set at P < 0.01 for all
analyses.
10
Results
A total of 60 patients were randomized into group A (n = 20),
group B (n = 20) or Group C (n = 20) (Figure 1 flowchart).
The demographic and clinical baseline characteristics of the 3
groups were well balanced (Table 1).
As regards primary outcome measures, 2-way ANOVA showed a
significant group (F=19.521; p<0.001) and time (F=66.129;
p<0.001) effect for VAS score while no significant group*time
interaction was found (F=2.708; p=0.03).
Post hoc analysis revealed that VAS scores were significantly
lower than baseline values at the end of the therapy. At this time,
however, patients in group C displayed the best results when
compared with other groups. Patients in group A and in group C,
but not those in group B maintained lower pain level at T2 than at
baseline, with significant lower VAS values in Group C (Table 2).
Two-way ANOVA showed a significant group (F=14.854;
p<0.001) and time (F=47.262; p<0.001) effect for Womac pain
11
subscale while no significant group*time interaction was found
(F=1.687; p=0.155). Post hoc analysis revealed that WOMAC
pain scores were significantly lower than baseline values at the
end of the therapy. At this time, however, patients in group C
displays the best results when compared with other groups.
Patients in all groups maintained lower pain level at T2 than at
baseline, with significant lower VAS values in Group C when
compared with Groups A and B (Table 2).
Regarding WOMAC joint stiffness scores, 2-way ANOVA
showed a significant group (F=8.521; p<0.001) and time
(F=13.344; p<0.001) effect for VAS score while no significant
group*time interaction was found (F=1.777; p=0.136). Post hoc
analysis revealed that WOMAC joint stiffness scores were
significantly lower than baseline values at the end of the therapy
and at 1-month follow-up in group B and C, but not in group A
(Table 2). A significant group (F=19.325; p<0.001) and time
(F=17.725; p<0.001), but not group*time interaction (F=1.961;
12
p=0.103) effect for WOMAC disability subscore was found.
WOMAC disability scores were significantly lower than baseline
values at the end of the therapy and at 1-month follow-up in group
B and C, but not in group A (Table 2).
As regards US measurements, the maximum axial area did not
change as a consequence of the treatment in any of the three
groups (F=1.334; p=0.259). Contrarily, sagittal area measurements
were influenced by time (F=10.027; p<0.01) at 2-way ANOVA.
Post hoc analysis revealed significant differences between preand post-treatment evaluation in Group B and Group C, but not in
Group A (Table 3).
Discussion
According to our results HT and aspiration, alone or in
combination, are effective in terms of pain relief and functional
improvement in a group of patients with knee OA complicated
with BC. Interestingly, however, the best results were obtained in
those patients in whom the therapies were administered in
13
combination (Group C). This is in line with other work that has
shown that the combination of different therapies improve both
pain and, consequently, function.16
Pain is an important factor restricting movement and functionality.
Theoretically, when pain decreases, muscle spasm decreases and
joint mobility and concomitantly function should increase.12,18 The
wall surface calculated in both axes was reduced in all cases after
injection, but the values in question were not significant.
Intra-articular injections of corticosteroids improve symptoms
associated with BC by reducing intracavitary pressure and helping
to resolve the flare16, although we have seen how the results of the
HT are superior about the pain and function at the first week but
no in terms of reduce surface of BC.
Although the reduction of the areas are not significant, this would
seem to reduce the only simple painful swelling in all groups.
Therefore, it seems to be more of a mechanical mechanism than
merely anti- inflammatory.
14
A recent survey among European specialists demonstrated that,
when orthopedic surgeons are faced with BC in adults, only 16%
employ aspiration as a first approach, whereas the majority of
specialists (37%) tend not to undertake any attempt to cure. The
majority of BCs are asymptomatic, but in a small percentage of
patients, complications and symptoms occur.19 Cyst aspiration
with corticosteroid injection gives pain relief and cyst volume
reduction
in
patients
with
BCs
and
concomitant
knee
osteoarthritis5. However, when compared with current literature,
the results are similar to those obtained through intra-articular
knee corticosteroid injection16. Therefore, when only a localized
painful swelling is present as a secondary complication of BC, we
consider it appropriate to perform not aspiration but only
corticosteroid injection or else HT. In effect in our case, the only
HT was more effective than US-guided aspiration and
corticosteroid injection in the BC in terms of both pain and
function. The HT is without risk for this aspect and is preferable to
15
the only US-guided aspiration and corticosteroid injection in the
BC.
There are many more complications of the simple painful swelling
which are described in the literature. These may include not only
popliteal veins and arteries, but also, in rare cases, cyst leakage
and compartment syndrome20,21. Probably the combination therapy
should be made when faced with this type of complications in
order to reduce the compressive effects caused by Baker’s Cyst.
The most important limitation of our trial was the lack of a longterm follow-up; as such, our results are applicable only for the
early stage to determine long-term effects on clinical and
ultrasound characteristics.
Our results show that the group with the best performance has
been combined therapy both, pain, function and dimension of BC.
However, it should be used only in special cases such as those
described above. This is also the case because it remains a
minimally invasive therapy and not without risk.
16
References
1)Handy JR: Popliteal cysts in adults: A review. Semin Arthritis
Rheum. 2001;31:108–18.
2)Stone KR, Stoller D, De Carli A, et al: The frequency of Baker’s
cysts associated with meniscal tears. Am J Sports Med. 1996; 24:
670–671,
3) Rupp S, Seil R, Jochum P, et al: Popliteal cysts in adults.
Prevalence, associated intraarticular lesions, and results after
arthroscopic treatment. Am J Sports Med. 2002; 30:112-5.
4) Del Cura JL. Ultrasound-guided therapeutic procedures in the
musculoskeletal system Curr Probl Diagn Radiol 2008;37:203-18.
5) Di Sante L, Paoloni M, Ioppolo F, et. Al: Ultrasound-Guided
Aspiration and Corticosteroid Injection of Baker’s Cysts in Knee
Osteoarthritis. Am. J. Phys.Med.Rehabil. 2010; 89:970-975
6) Adler RS, Sofka CM: Percutaneous ultrasoundguided injections
in the musculoskeletal system. Ultrasound Q. 2003;19:3–12.
17
7) Rutjes AW, Nüesch E, Sterchi R, Kalichman L, Hendriks E,
Osiri M, Brosseau L, Reichenbach S, Jüni P.
Transcutaneous electrostimulation for osteoarthritis of the knee.
Cochrane Database Syst Rev. 2009; 7:CD002823.
8) Philadelphia Panel. Philadelphia Panel evidence-based clinical
practice guidelines on selected rehabilitation interventions for
knee pain. Phys Ther. 2001; 81:1675-700.
9) Johnson MI, Tabasam G (2002) A single-blind placebocontrolled investigation into the analgesic effects of interferential
currents on experimentally induced ischemic pain in healthy
subjects. Clin Physiol Funct Imaging.22:187–196.
10)
Cheing
GL,
Hui-Chan
CW.
Analgesic
effects
of
transcutaneous electrical nerve stimulation and interferential
currents on heat pain in healthy subjects. J Rehabil Med.
2003;35:15-9.
11) Zambito A, Bianchini D, Gatti D, et al. Interferential and
horizontal therapies in chronic low back pain due to multiple
18
vertebral fractures: a randomized, double blind, clinical study.
Osteoporosis Int. 2007;18:1541-5.
12) Cheing GL, Hui-Chan CW, Chan KM. Does four weeks of
TENS and/or isometric exercise produce cumulative reduction of
osteoarthritic knee pain? Clin Rehabil. 2002;16:749-60.
13) Altman R, Asch E, Bloch D, et al: Development of criteria for
the classification and reporting of osteoarthritis. Classification of
osteoarthritis of the knee. Diagnostic and Therapeutic Criteria
Committee of the American Rheumatism Association. Arthritis
Rheum. 1986;29:1039–49.
14) Kellgren JH, Lawrence JS: Radiological assessment of
osteoarthritis. Ann Rheum Dis. 1957;16:494–502.
15) Salaffi F, Leardini G, Canesi B, et al: Gonorthrosis and
Quality Of Life Assessment (GOQOLA). Reliability and validity
of the Western Ontario and McMaster Universities (WOMAC)
Osteoarthritis Index in Italian patients with osteoarthritis of the
knee. Osteoarthritis Cartilage. 2003;11:551-60.
19
16) Acebes C, Olga S, Dìaz-Oca A, et al: Ultrasonographic
Assessment of Baker’s Cysts after Intra-articular
Corticosteroid Injection in Knee Osteoarthritis. J Clin Ultrasound.
2006;34:113-7.
17) Law PP, Cheing GL, Tsui AY Does transcutaneous electrical
nerve stimulation improve the physical performance of people
with knee osteoarthritis? J Clin Rheumatol. 2004;10:295-9.
18) Cheing GL, Hui-Chan CW. Would the addition of TENS to
exercise training produce better physical performance outcomes in
people with knee osteoarthritis than either intervention alone?.
Clin Rehabil. 2004;18:487-97.
19) Fritschy D, Fasel J, Imbert JC, et al: The popliteal cyst. Knee
Surg Sports Traumatol Arthrosc. 2006;14:623-8.
20) Ozgocmen S, Kaya A, Kocakoc E, et al: Rupture of Baker's
cyst producing pseudothrombophlebitis in a patient with Reiter's
syndrome. Kaohsiung J Med Sci. 2004; 20:600-3.
20
21) Zhang WW, Lukan JK, Dryjski ML: Nonoperative
management of lower extremity claudication caused by a Baker's
cyst: case report and review of the literature. Vascular.
2005;13:244-7.
FIGURE LEGENDS
Figure 1: Schematic presentation of patient Flow-chart at one
month follow-up
Table 1 : Baseline characteristics of the study groups A, B and C
before the treatment (T0). Mean of number, age men, VAS,
WOMAC scores and areas of BC.
Table 2 : Comparison of pain level as measured by visual analog
scale and of WOMAC sub-scales scores before and after treatment
and at 1-Month follow-up in the three groups. Group A:
corticosteroid injection. Group B: Horizontal Therapy. Group C:
corticosteroid injection + Horizontal Therapy. P values are in bold
when significant. 1: Comparison between before and after
21
treatment within each group. 2: Comparison between after
treatment and 1-month follow-up within each group.
Table 3 : Comparison of sagittal and axial areas before and after
treatment and at 1-Month follow-up in the three groups. Group A:
corticosteroid injection. Group B: Horizontal Therapy. Group C:
corticosteroid injection + Horizontal Therapy. P values are in bold
when significant. 1: Comparison between before and after
treatment within each group. 2: Comparison between after
treatment and 6-month follow-up within each group.
Tab.1
Group 1
Group 2
Group 3
NUMBER
20
20
20
Age men
70,50 (7,6)
70,80 (7,4)
70,50 (8,3)
Grade II
11
10
8
Grade III
9
10
12
VAS baseline
6,23(1,3)
6,89(1,1)
6,09(1,5)
WOMAC A
baseline
5,15(2,7)
5,39(1,7)
4,97(0,9)
WOMAC B
4,44(2,1)
5,05(1,8)
4,25(2,2)
WOMAC C
5,15(2,7)
6,33(1,5)
4,47(2,2)
Sagital
5,07(1,9)
6,52(1,9)
5,01(1,8)
Axial
1,90(1,0)
1,68(1,3)
1,67(0,8)
Kellgren–
Lawrence
Area:
22
Tab. 2
Pain (range 0-10)
Before treatment
After treatment
p1
Follow-up
P2
WOMAC A
Before treatment
After treatment
p1
Follow-up
P2
WOMAC B
Before treatment
After treatment
p1
Follow-up
P2
WOMAC C
Before treatment
After treatment
p1
Follow-up
P2
Group A
Group B
Group C
A vs B
B vs C
A vs C
6.23 (1.3)
4.13 (1.5)
<0.00001
4.09 (1.3)
0.99
6.89 (1.1)
4.17 (1.6)
<0.00001
5.41 (1.3)
0.01
6.09 (1.5)
2.7 (1.5)
<0.00001
2.95 (1.3)
0.84
0.29
0.99
0.95
0.003
0.17
0.004
0.009
0,000
0.003
5.15 (2.7)
3.82 (1.1)
0.0009
3.79 (1.5)
0.99
5.39 (1.7)
3.07 (1.8)
0.0000
3.74 (1.7)
0.31
4.97 (0.9)
2.02 (1.5)
0.0000
2.02 (1.4)
1.0
0.95
0.24
0.63
0.06
0.44
0.0005
0.99
0.0008
0.0006
4.44 (2.1)
4.05 (2.5)
0.79
3.74 (2.0)
0.85
5.05 (1.8)
3.01 (1.6)
0.002
3.63 (1.7)
0.83
4.25 (2.2)
1.89 (1.0)
0.0002
2.27 (0.8)
0.79
0.54
0.17
0.35
0.13
0.95
0.0009
0.98
0.05
0.03
5.15 (2.7)
4.11 (2.3)
0.21
4.80 (1.5)
0.50
6.33 (1.5)
3.5 (2.2)
0.0001
4.92 (2.4)
0.06
4.47 (2.2)
2.02 (1.6)
0.0004
2.14 (1.2)
0.98
0.15
0.59
0.01
0.04
0.52
0.003
0.98
0.0001
0.0001
Group A
Group B
Group C
A vs B
B vs C
A vs C
5.07 (1.9)
3.87 (1.1)
0.30
3.44 (2.1)
0.86
6.52 (1.9)
3.96 (2.6)
0.005
4.48 (2.4)
0.79
5.01 (1.8)
3.04 (2.3)
0.04
3.65 (4.3)
0.73
0.17
0.99
0.15
0.49
0.99
0.56
0.41
0.56
0.96
1.9 (1.0)
1.51 (0.9)
0.59
1.11 (0.7)
0.58
1.68 (1.3)
1.55 (1.0)
0.83
1.87 (1.1)
0.71
1.67 (0.8)
1.14 (1.1)
0.39
1.71 (2.5)
0.33
0.12
0.99
0.89
0.56
0.84
0.63
0.14
0.92
0.29
Tab. 3
Sagittal Area
Before treatment
After treatment
p1
Follow-up
P2
Axial Area
Before treatment
After treatment
p1
Follow-up
P2
23
Figure : Flow-chart diagram of the study.
Assessment for elegibility
(n=70)
Refuse to participate
(n=3)
T0: clinical and US
evaluation (n=67)
Not meeting inclusion
criteria (n=7)
Randomization (n=60)
Group A
Allocated (n=20)
Received to
intervention
(n=20)
Group B
Allocated (n=20)
Received to
intervention
(n=20)
Group C
Allocated (n=20)
Received to
intervention
(n=20)
T1: analyzed (n=20)
T1: analyzed (n=20)
T1: analyzed (n=20)
T2: analyzed (n=20)
T2: analyzed (n=20)
T2: analyzed (n=20)
24
Index
Introduction………………………………….....2
Methods………………………………….……..4
Study design………………………………………...5
US Evaluation………………………………………6
Clinical Evaluation…………………………………7
Statistical Analysis………………………...………10
Results……………………………………………...11
Discussion………………………………………….13
References…………………………………………17
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