Dorsal root ganglionectomy for pseudotumor of the L3 dorsal root ganglion: a rare case and a rare treatment

Dorsal root ganglia are oval enlargements on the dorsal nerve roots and contain the cell bodies of sensory neurons. Asymmetry of dorsal root ganglia may occur naturally, yet natural occurrence of gigantic dorsal root ganglion (DRG) is rare. The patient was 61-year-old woman who presented with atypical symptoms like neuropathic pain and urinary distention. Neuroimaging has shown left L3-4 far-lateral disc herniation and a gigantic L3 DRG. At surgery, the dural sheath of the ganglion had to be opened and a firm, yellow-colored abnormal tissue was exposed. The abnormal tissue considered to be a tumor of neural origin was gross totally excised and the patient’s symptoms ceased immediately after surgery. Histopathological examination of the specimen revealed nothing more than normal DRG morphology. At 4 months postoperatively, the patient is well with mild L3 hyperesthesia and hyperalgesia. Dural sheath opening in neurosurgery is not a routine practice. The sheath may need to be opened when surgeon suspects of a tumor, a free disc fragment and any inflammation within the ganglion. Operative morphology of a severely edematous but non-tumoral (pseudotumor) ganglion has not previously been documented.
Introduction
Small neoplastic lesions of the vertebral column and the spinal canal are often misdiagnosed as intervertebral disc disease owing to the commoner occurrence of the latter [1]. Rarely, a neoplastic lesion may coincide with a herniated intervertebral disc usually without a topographic relationship in between [8]. Concomittant appearance of a disk herniation and a neoplastic lesion compromising the same nerve root represent a unique situation [1]. We herein report the unique case of a pseudotumor of the L3 dorsal root ganglion (DRG) adjacent to a far-lateral L3-4 disc herniation.
Case history
A 61-year-old physician presented with excruciating pain in her left leg. The mild leg pain that has been around the left knee and around the posterior hip for some weeks suddenly became unbearable one afternoon. The patient came to emergency room 8 h after the onset of the pain. Upon further questioning, the patient confessed that she had not emptied her bladder since the pain started. Past medical history was positive for a distant episode of trigeminal neuralgia, cluster headache, and an episode of significant back and right leg pain 7 years ago and a recent pulmonary embolus. Past surgical history included total hysterectomy and bilateral salpingo-oopherectomy after a serious pelvic inflammatory disease and abscess formation within the uterine tube.
In the emergency room, the patient was in extreme pain. Any movement or touch would exacerbate the pain. Right leg-raising test was positive at 60 and left leg-raising test was positive at 20°. Power was normal in both legs, including knee extension. Patellar and the ankle reflexes were normoactive bilaterally. Abdominal examination for a distended bladder was fruitless because of softened subcutaneous fat. Lumbar MR showed disc degeneration and mild bulging at L3-4, L4-5 and L5-S1 levels yet at L3-4 level there was foraminal and a round extraforaminal disc herniation (Fig. 1a, b). Lumbar MR scan also verified a fully distended bladder (Fig. 1c). Considering vaque radiological findings in contrast to serious pain and urinary retention, the MR examination was extended to cover the whole cervico-thoracic and thoracic levels. There was no cord compression.
Fig. 1Axial T1-weighted (a) and T2-weighted (b) MR scans through L3-4 interspace show an extraforaminal lesion with questionable continuity with the disc space. The lesion is isointense on both T1- and T2-images. Please note that on T2-weighted axial image (b), the contralateral dorsal root ganglion (DRG) shows intermediate to high signal. c Parasagittal MR scan show L3-4 disk herniation obliterating the left neural foramen anteroinferiorly.Yet the left L3 nerve is of same width as the roots one above or below. d Parasagittal MR scan 5 mm lateral to section c shows that the enlarged DRG (arrows) appears to have been stuck in the distal neural foramen. Please note that the fat plane around the DRG is totally obliterated
The next morning, urinary retention re-occurred and an indwelling urinary catheter had to be placed. An ultrasound of the abdomen and pelvis was not contributory except identification of few benign adhesions secondary to previous pelvic surgery and a distended gall bladder. Meanwhile the left knee pain and the left sciatica got only a bit better but the patient described additional occasional electric shock like pain radiating medially from the left groin to the left knee. Lumbar computerized tomography (CT) to rule out a small bone chip originating from end-plate attached to a free disc fragment was done next. Axial CT scans showed the presence of a left-sided round hyperdense extraforaminal lesion at L3-4 level that was reported to be consistent with far-lateral disc herniation (Fig. 2a). Coronal reformatted CT images better demonstrated the lateral extent of the disc herniation (Fig. 2b). After an unsatisfactory 2-day narcotic treatment with codein 60 mg q6h, gabapentin 300 mg twice a day was started. On the third day of admission, a new pain emerged around the left inguinal area. By this time, the left patellar reflex diminished and left knee extension got 20% weaker. IV steroid (80 mg methyl prednisolon as the loading and 40 mg twice a day as the maintenance dose) was then started. Steroid alleviated a significant portion of the pain. Tapering steroid dose immediately caused return of intense pain, so surgery was considered as the last resort.
Fig. 2Axial CT image through the lower end-plate of L3 (a) and coronal reformatted CT (b) image show a round hyperdense extraforaminal lesion consistent with far-lateral disc herniation
The patient was informed to consent for the removal of far-lateral disc herniation at L3-4 level. After medial facetectomy and ligamentous removal, the left L4 nerve and the L3-4 disc space were exposed. The bulging disc was compressing the L4 root from its shoulder. After standard discectomy, the L4 root became mobile. Next, lateral disc space was emptied by angling the rongeur laterally. Yet, disc compression alone was far from explaining the dramatic clinical picture. After total removal of left L3 inferior facet and L4 superior facet and undercutting the L3 pedicle, the left L3 root was identified and traced laterally. L3 nerve was more or less normal sized yet L3 DRG was extremely different than normal. The DRG was 3–4 times bigger than a normal DRG. The L3 root was totally immobile (Fig. 3a). The DRG felt extremely gritty. The dural sheath of nerve root and the DRG was opened. A yellow-colored firm tissue came into view (Fig. 3b, c). There was good cleavage from the dural sheath and the underlying septum. The healthy ventral rootlets were pushed anteriorly and inferiorly by the mass (Fig. 3d). Overall, the mass lesion within the root sleeve was totally extirpated. Although no cerebrospinal fluid (CSF) was seen in the operative field, the dural sheath was sutured with interrupted prolene sutures and the suture was reinforced with tissue fibrin glue. On postoperative day 1, the urinary catheter was removed and the patient emptied her bladder spontaneously. The original pain was totally gone. The left knee function returned to normal. On third postoperative day, she complained of mild hyperesthesia and hyperalgesia over the left knee which did not affect her daily life. At 4 months postoperatively, she is leading a normal life with gabapentin 300 mg twice a day.
Fig. 3Operative microphotographs show that: a the left L3 root and the DRG are extremely swollen, b after opening the dural nerve sheath, the upper end of a yellow colored tumor is being dissected, c the lower end of the tumor is being dissected with better cleavage, d after the removal of the tumor normal appearing ventral motor rootlets come into view, e root size return to normal after suture closure of the dural sheath (black arrows)
The histopathological specimen was extensively studied and did not reveal anything other than normal DRG tissue with mature ganglion cells, axons and Schwannian stroma supporting the axons (Fig. 4).
Fig. 4Photomicrographs a with hematoxylin and eosin and b with neurofilament (NF) protein immuno-stain demonstrate axons (left) and ganglion cells dispersed in a cellular stroma consisting of bundles of elongated spindle cells (right) (×200 original magnification). This represents normal DRG morphology
Discussion
Dorsal root ganglia are oval enlargements on the dorsal nerve roots and contain the cell bodies of sensory neurons. Although both the DRG and the ventral motor root are surrounded by a common dural sheath, a thin fibrous septum separates both. The DRG are surrounded by fat within the intervertebral foramen. According to the baseline anatomic information that Hasegawa et al. [5] obtained from male volenteers using MRI, the mean width, length and height is 5.7×7.1×7.3 mm3 for L3 DRG, 6.2×8.4×8.2 mm3 for L4 DRG, 5.9×9.4×8.3 mm3 for L5 DRG and 6.2×11.2 mm2 for S1 DRG, respectively (data on the height of S1 DRG was not given in this study). The lower was the spinal level, the bigger was the ganglion size. In that study, the DRGs were located in lumbar intervertebral foramen in 92% of L1, 98% of L2, 100% of L3 and L4 and 95% of L5 levels. The S1 DRG was intraspinal in 79%. However analyzing patients presenting with low-back pain or sciatica, Hamanishi and Tanaka [4] found that 100% of L2 DRG, 48% of L3 DRG, 27% of L4 DRG and 12% of L5 DRG were located extraforaminally while 52% of L3 DRG, 72% of L4 DRG and 75% of L5 DRG were located intraforaminally.
Preoperative radiological diagnosis of spinal nerve tumors producing radiculopathy or masquerading as spinal and/or root pain has been facilitated by combined use of CT and MR. Intradural extramedullary tumors like schwannoma or extradural tumors like neurofibroma frequently affect the DRG and appear as dumbbell-shaped in 15% of cases [10, 14]. Diagnosis of tumors that had already enlarged the neural foramen is usually straightforward. However, a smaller pathology intrinsic to the root or the DRG will first be expected to cause an asymmetry as also depicted by MR scans in our patient. Yet asymmetry of DRGs may also occur naturally [4]. Hamanishi and Tanaka [4] found asymmetrical locations and sizes in 11% of the reviewed DRGs. Asymmetry at L3-4 level is rarer. Out of 104 patients that they reviewed, only one had DRG asymmetry at L3-4 level. Two cases who had asymmetrically gigantic DRGs similar to our case underwent surgery at different spinal levels [4]. In the first case, the lowered pedicle appeared to push down and kink the intraspinal portion of the L5 DRG. In the second case, the mass mimicking the gigantic DRG was histologically confirmed to be very old sequesterated nucleus pulposus at L5-S1 level. However, anteriorly compressed DRG could not be detected by MR scan at all [4].
As for MR signal intensity, schwannomas and neurofibromas will often appear iso- to hypointense on T1- and hyperintense on T2-weighted MR images [14]. The left L3 DRG in our case appeared isointense on both T1- and T2-weighted MR images. Intermediate signal on T2-weighted MR image usually suggests the presence of a tumor with numerous cellular and fibrous components and very little myxoid stroma. Unfortunately, paramagnetic contrast was not given in our case. One can argue that the preoperative radiological diagnosis of a tumor could have been possible if intravenous gadolinium was given. Although gadolinium enhanced MR imaging allows for better detection of intraneural edema with diffuse enhancement along the involved nerve roots, this characteristic probably would not have helped us in diagnosing a DRG tumor since DRG always enhance with contrast medium because of a less developed blood–nerve barrier anyway. Recently, a French group studying enhancement pattern on 180 healthy DRG also concluded that 100% demonstrated significant and homogenous enhancement [3]. Therefore, even if we had used intravenous paramagnetic contrast preoperatively, it would probably be impossible to differentiate between an intraradicular tumor and a healthy DRG.
It was only at surgery that the left L3 DRG was found to be extremely swollen and had to be opened. A nerve root and a DRG may become swollen because of both biochemical irritation of nucleus pulposus and the mechanical compression of the disc materal [2, 6]. The mechanical compression of the DRG can increase the endoneural fluid pressure within the DRG almost threefolds [11]. Yet since the dural sheath is not an elastic tissue, a DRG can hardly ever reach the gigantic size that we have observed. Morever, the far-lateral disc protrusion at L3-4 level observed at surgery (in contrast to the extent of the herniation as seen on CT and MR images) could not have exerted the force necessary to cause a significant endoneural fluid pressure rise within the left L3 DRG. Therefore, the adjacent far-lateral disc herniation probably just coexisted with the gigantic left L3 DRG of unknown origin and served a better purpose by attracting our surgical attention to this part of the spine. Not only the size of the involved DRG, but also its firm feeling suggested the presence of something unusual inside it. Although intraradicular disc herniations occur more commonly at L5-S1 and L4-5 levels [12], the surgeon’s impression before the microsurgical opening of the dural sheath was more inclined to a rare intradicular disc herniation rather than a tumor.
Dural opening in similar cases totally depend on surgeon’s experience and/or attitude or on the medicolegal restrictions of the preoperative consenting procedure. By opening the dural sheath of a nerve root or a DRG the surgeon not only will prolong the operative procedure but also will take the morbidity risk associated with CSF leak and difficulty with wound healing. Moreover, extra expense of tissue fibrin glue and/or external lumbar drainage may also trigger an hesitation before dural opening in the currently managed health care systems. If a gross pathology like a tumor or a disc fragment is not readily encountered between the rootlets, chances are histopathology will be the only diagnostic tool. In addition to a real mass lesion like tumor or disc material, inflammatory reactions within a DRG—although very rare—may also cause a tumor-like lesion. A team from Tübingen, Germany recently has reported a very similar case presenting with low back pain and progressive hypesthesia of the thigh [10]. MR imaging with contrast enhancement revealed an intraspinal–extradural mass at L1-2 level compressing the right L2 root. The surgical part of their case is almost identical to ours. The surgical team emptied the disc and the nerve was still compressed and appeared to be enlarged. In the end, they had to open the dural sheath and resect the indurated and swollen part of the ganglion. Histopathological diagnosis was ganglionitis characterized by loss of ganglion cells, increased number of nodules of Nagcotte and diffuse infiltration of T cells.
Ganglionectomy as performed for cancer pain or non-cancer pain (for failed back surgery syndrome or chronic lumbar radiculopathy) was originally described by Osgood et al. [9] and by definition is an extradural operation [13]. Wilkinson and Chan [15] in their recent publication advocated the use of microscope for the procedure. After exposure of the ganglion and surrounding plexus and compression of the venous plexus with cottonoids, the longitudinal incision path along the dural sheath is coagulated using low-current bipolar. Once the dural sheath is incised dorsally using a no. 11 knife, ganglion tissue will come into view. Young [16] described the DRG as a round, yellow, irregular structure. Wilkinson and Chan [15] described the ganglion as having an appearance similar to fat, with tiny “sparkles” within. The latter description is for ganglia from patients with failed back surgery syndrome or chronic lumbar radiculopathy. In rare circumstances like we had, differentiation between an healthy and a tumoral ganglionic tissue may be extremely difficult even with the operating microscope. At this stage, the surgeon has to decide between a biopsy or total removal of the abnormal looking ganglionic tissue. Biopsy may be safer but then there is the possibility of sampling error. If total removal of the DRG is aimed (sensory ganglionectomy), then the afferents and efferents of the ganglion are elevated first and then the ganglion is separated from the underlying septum. To lessen the likelihood of neuroma formation, the proximal end of the ganglion is either hemoclipped or cut with CO2 laser [7]. If leakage of CSF is not encountered (which usually is the case) a watertight closure of the perineurium is not necessary. Some even advocated to leave an autogenous fat graft in the surgically created defect [15]. As for complication of the procedure, deafferentiation pain has been exaggerated because it is usually transient and never reaches to the point of anesthesia dolorosa [13, 15]. Taha et al. [13] states that there is no uniformly beneficial treatment for deaffarentiation pain after ganglionectomy but our patient definitely benefited from brief use of gabapentin.
In conclusion, we reported the unique case of a pseudotumor of L3 DRG. The patient presented with atypical symptoms like neuropathic pain and urinary distention. Preoperative MR scans showed a gigantic left L3 DRG yet this asymmetry was masked by the presence of an adjacent ipsilateral far-lateral disc herniation. Attention to foraminal and extraforaminal part of the spine is of utmost importance in the evaluation of lumbar MR scans. Surgery was both diagnostic and therapeutic in this case. Before opening the dural sheath of a nerve root or DRG, a surgeon should realize that if a tumor or a disc fragment does not come out at once, then it may only be through histopathology that a proper diagnosis can be reached.

dorsal root ganglion
ganglionectomy
magnetic resonance imaging
microsurgery


Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

Background Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated.
Optimum treatment strategies for locally advanced soft tissue sarcoma (STS) of the extremities have evolved considerably over the past 25 to 30 years. In 1982, Rosenberg et al.1 showed that amputations or exarticulations of the affected limb do not result in higher survival rates. This made preservation of the extremity and good limb function all the more important.2,3 An established limb salvage strategy is to perform a hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan, followed by delayed tumor resection and, in case of marginal or nonradical resection, by adjuvant external-beam radiotherapy (EBRT).4,5 Although ILP, in which high doses of chemotherapy are regionally delivered, is a technically demanding operative procedure, amputation necessitated by peri- or postoperative surgical complications occurs in <1% of cases.4 On the other hand, patients undergoing an intentionally limb-saving treatment with ILP still have a short- or long-term risk up to 40% of loss of the affected limb due to massive necrosis of the tumor and overlying skin resulting in a soft tissue deficit, late local recurrence, or critical leg ischemia.5
In ILP, cytotoxic agents are used, which cause a local toxic effect in the perfused extremity. After investigation of several perfusion agents for STS, the two-drug regimen of TNF-α and melphalan turned out to be highly effective.4 The pathological tumor microvascularization is the primary target for TNF-α, resulting in coagulative and hemorrhagic necrosis of the tumors.6 Olieman et al.7 demonstrated by angiography findings of specific destruction of tumor vessels after perfusion with TNF-α, leaving the normal vasculature unchanged. The surgical procedure of ILP, however, exposes the cannulated blood vessels to intravascular manipulation, by means of arteriotomy, venotomy, and the insertion of catheters. Consequently, a 1% to 10% risk of developing acute vascular complications, such as thrombosis at the arteriotomy site and deep-vein thrombosis (DVT), has been described in the literature.8–10 Moreover, chemotherapy and atherosclerosis risk factors could have a synergistic role on the development of arterial stenosis.11 Adjuvant EBRT leads to a high incidence of early and late morbidity. Long-term vascular side effects, in particular arterial stenosis, can be induced by radiotherapy.12–14
Because little is known with respect to the late vascular morbidity of the combined procedure of ILP and EBRT, a retrospective study was conducted to evaluate the long-term locoregional vascular side effects of ILP, followed by delayed surgical resection and adjuvant high-dose EBRT.
PATIENTS AND METHODS
From 1991 to 2003, a total of 73 patients with a median age of 54 (range, 14–80) years and with locally advanced STS underwent 77 perfusions with a combination of TNF-α and melphalan, with (n = 19) or without (n = 58) interferon gamma at the Division of Surgical Oncology of the University Medical Center Groningen, University of Groningen. The perfusion technique has been previously extensively described.15,16 Perfusion was followed by delayed local resection of the tumor remnant, and in cases of marginal or microscopically positive resection margins, high-dose postoperative EBRT was considered.
In 2005, 39 patients were still alive and in follow-up. Information about their past and current oncological and vascular status was obtained from the follow-up notes in the medical records. Seven patients were unable to participate in the study because of severe or advanced morbidity or comorbidity (n = 2) or because of nonmedical reasons (n = 5). Consequently, 32 patients, 14 men (44%) and 18 women (56%), with a median age of 47 (range, 14–71) years, were included (response rate, 82%). They completed a vascular checklist that asked questions about their medical vascular history, and they were screened for risk factors of vascular disease, such as smoking, hypertension, and diabetes. A blood sample was drawn to determine the cholesterol spectrum, which was used as an indicator of risk for atherosclerosis. All patients underwent a noninvasive arterial and venous vascular work-up that comprised duplex ultrasonography and vascular pressure measurements. The ankle-brachial index (ABI) and pulsatility index (PI), which are indications of vascular blood flow velocity, were measured to indicate the arterial status of the limb. For evaluation of veins, ultrasonography was performed to detect DVT and insufficiency. All investigations were performed by the same examiner (J.L.).
Five patients had a STS of the upper extremity (16%) treated with axillary perfusion. The remaining 27 patients had a STS located in the lower limb (84%) and were treated with iliac (n = 13, 41%), femoral (n = 5, 16%), or popliteal (n = 9, 28%) perfusion. There were 27 primary STS and 5 recurrent STS. Twenty-four patients (75%) received adjuvant 60 to 70 Gy EBRT in fractions of 2 Gy. Adjuvant systemic chemotherapy was provided to seven patients. Definite histopathological classification of tumor (one embryonal rhabdomyosarcoma and one extraossal osteosarcoma) was the reason in two patients; three patients were treated with chemotherapy because they participated in an European Organization for the Research and Treatment of Cancer trial (EORTC 62931). Two patients received chemotherapy in a palliative setting for distant metastasis. All patients were treated after informed consent was obtained according to institutional guidelines. Twelve different histological types of STS were distinguished. The pathological grade of the tumor was scored following the criteria of Coindre et al.,17 and the stage of the tumor was assigned according to the American Joint Committee on Cancer.18 Patient and tumor characteristics are summarized in Table 1.
TABLE 1.Characteristics of patientsAge (y)SexDiseaseLocalizationHistologyGradeAJCC stageLevelEBRTAmputationFollow-up (mo)18FPrimaryUpper legEmbryonal rhabdomyosarcoma33IliacNN15944FRecurrentPopliteal fossaMyxoid liposarcoma11IliacYN15243MPrimaryUpper legSynovial sarcoma33IliacYN15118MPrimaryLower legMyxoid chondrosarcoma23PoplitealYY14948FPrimaryUpper legWell differentiated liposarcoma11IliacYN14356FPrimaryProximal tibiaPNET33IliacYY13750FRecurrentFootPUS33PoplitealNN13525FPrimaryPopliteal fossaSynovial sarcoma23PoplitealYN13244MPrimaryUpper legMyxoid liposarcoma11IliacYN13124MRecurrentLower legSynovial sarcoma23PoplitealYN12937FPrimaryElbowMPNST23AxillaryYN12148MPrimaryPopliteal fossaMyxoid liposarcoma23IliacYN11163FRecurrentLower legPUS23PoplitealNY10737MPrimaryUpper legMyxoid liposarcoma11IliacYN10558MPrimaryUpper legPUS23IliacYN9871FPrimaryUpper legLeiomyosarcoma11FemoralNN9445FPrimaryUpper legPUS33IliacNN8256FPrimaryLower legPUS33PoplitealYN6163MPrimaryPopliteal fossaMyxoid chondrosarcoma3FemoralYN5037FPrimaryKneeLeiomyosarcoma11FemoralYN3628MPrimaryPopliteal fossaSynovial sarcoma23FemoralYN3657FPrimaryUpper legPUS33FemoralYN3542FPrimaryKneeSynovial sarcoma23IliacYY3247FPrimaryArmPUS33AxillaryYN3058FPrimaryLower legPUS33PoplitealYN2627MPrimaryArmEpithelioid sarcoma34AxillaryYN2671MRecurrentArmMyxoid fibrosarcoma11AxillaryNN2456FPrimaryArmExtraosseal osteosarcoma33AxillaryNN2214MPrimaryLower legPUS33PoplitealYN2065FPrimaryFootSynovial sarcoma23PoplitealNY1863MPrimaryUpper legSynovial sarcoma33IliacYN1771MPrimaryUpper legRhabdomyosarcoma33IliacYN17AJCC, American Joint Committee on Cancer; EBRT, external-beam radiotherapy; PNET, primitive neuroectodermal tumor; PUS, pleomorphic undifferentiated sarcoma; MPNST, malignant peripheral nerve sheath tumor.
The results were statistically analyzed by the Wilcoxon rank test and the Mann-Whitney U-test. Values of P ≤ .05 were considered significant. SPSS 12.0.1 for Windows statistical software was used (SPSS, Chicago, IL).
RESULTS
Before ILP, none of the patients had a history of cerebrovascular insufficiency, coronary artery disease, peripheral arterial occlusive disease, or any other vascular disease. Risk factors for cardiovascular disease, hypertension, diabetes, smoking, obesity, hypercholesterolemia, and familiar arterial occlusive disease were analyzed (Table 2).
TABLE 2.Risk factors for atherosclerosisRisk factorn%Dutch population (%)Hypertension10319.9a,bDiabetes mellitus4133.1bSmoking29.6b  Smokers928  Former smokers1031BMI  BMI >25.0175346.5b  BMI >30.041310.9bHypercholesterolemia (total cholesterol >6.5)61914cFamiliar cardiovascular disease1444NABMI, body mass index; NA, not available.a Range, 5% to 45%.b From http://www.cbs.nl/.c From http://www.hartstichting.nl/.
Two patients underwent vascular reconstruction after en-bloc tumor resection with the artery. One patient underwent a reconstruction of the femoral artery with an infragenual femoral-popliteal bypass, and the second patient underwent a popliteal artery reconstruction with an autologous vein graft. A DVT in the lower leg was diagnosed in the postoperative period in three patients (7.7%).
Nine (23%) of the 39 alive patients underwent a lower limb amputation at different levels after ILP with or without EBRT. No amputations of the upper extremity were performed. In two patients with microscopically involved resection margins, an amputation of the affected limb was indicated because adjuvant radiotherapy was contraindicated. One patient underwent amputation due to tumor recurrence 18 months after ILP and EBRT. Amputation was performed for critical leg ischemia due to atherosclerosis in two patients at 110 and 125 months after ILP and EBRT. Because of severe obstruction of the crural vessels, reconstructive therapy was not suitable.
The other four amputations were performed for extensive postperfusion necrosis of the involved tumor site (three patients at 0, 8, and 12 months after ILP with or without EBRT) and arterial occlusion without any vascular reconstructive possibilities (one patient 15 months after ILP and EBRT).5[A1] Figure 1 illustrates treatment, outcome, and reasons for amputation. Five of the 32 patients included in this study underwent amputation and could therefore only partially undergo vascular follow-up.
FIG. 1.Flow chart illustrating treatment, outcome, and reasons for amputation. EBRT, external-beam radiotherapy; AMP, amputation; NI, not included in this study.
Arterial Vascular Disease
With a median follow-up of 88 (range, 17–159) months, no patient experienced peripheral arterial occlusive disease. With duplex ultrasonography, however, two patients showed a complete arterial occlusion at the level of cannulation (6%). One of them underwent an iliac perfusion and EBRT because of a STS of the lower leg in 1993. After 10 years, she had signs of critical leg ischemia, which required a transfemoral amputation. She is now free of pain and can walk with a well-functioning prothesis. The other patient showed an axillary occlusion 10 years after an axillary perfusion, followed by resection and EBRT at the forearm. She did not have any symptoms of arterial occlusive disease, and her arm functions normally. Duplex ultrasonography showed good collateral flow. Two other patients (6%) showed an arterial stenosis at cannulation level at 22 and 30 months after axillary perfusions, followed by EBRT at the upper arm and axilla in one and systemic chemotherapy in both patients. They had normal arm function without any signs of ischemia.
The arteries at resection level were also evaluated. One patient with a fossa poplitea STS had complete occlusion of the superficial femoral artery 6 years after ILP and EBRT, with open arteries below knee level. A femoral-popliteal bypass was considered but was not performed because of the absence of any symptoms. At the time of evaluation, the ABI was .50; the patient did not have any complaints besides compression ulcers on his feet, which responded well to conservative therapy. The patient who needed an autologous vein graft of the popliteal artery has a stenosis at this level without clinical signs of arterial occlusive disease.
Twenty-two of the total 32 patients included underwent ABI measurements; 22 had their PI determined at the femoral level and 20 at the popliteal level. Five patients were excluded because of amputation of the limb; another five were excluded because of a STS located in the upper limb. Of the remaining 22 patients, 18 received postoperative EBRT for the above-described indications.
In 21 of 22 patients, the ABI (normal, ≥1.00) in the treated leg was .91 or more. As mentioned above, one patient had an ABI of .50 without any complaints. ABI measurements in the involved leg (median, 1.02; range, .50–1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91–1.36; P = .001). Seven patients showed a decreased femoral PI (normal range, 5–10). Six of them underwent an iliac perfusion (86%). Popliteal PI (normal range, 6–12) was decreased in six patients. Perfusion at a more proximal level was performed in four of these patients (67%). When compared with the contralateral leg, PI was lower in the treated leg in 17 of 22 patients at femoral level (median, 6.30; range, 2.1–23.9 vs. median, 7.35; range, 4.8–21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0–21.4, vs. median, 1.95; range, 8.0–32.6; P < .0005) (Table 3). There were no differences in objective vascular side effects between men and women, between patients who did or did not undergo EBRT, or between patients <50 years old versus older patients (Table 4). In patients with a follow-up period of >5 years, there was more often a decrease in ABI, compared with patients with shorter follow-up (13 of 14 patients vs. 4 of 8 patients, P = .024). With a longer follow-up period, there was also more often a decrease in PI at the femoral level (13 of 14 patients vs. 3 of 7 patients, P = .024), but not at the popliteal level (12 of 12 patients vs. 7 of 8 patients, P = .221) (Table 5). No patient required vascular intervention during follow-up.
TABLE 3.Results of ankle-brachial index (ABI) and pulsatility index (PI) measurements in lower extremities of 22 patientsIndexTreated extremity, median (range)Contralateral extremity, median (range)P valueABI1.02 (.50–1.20)1.090 (.91–1.36).001PI femoral6.30 (2.1–23.9)7.35 (4.8–21.9).011PI popliteal8.35 (.0–21.4)10.95 (8.0–32.6)<.0005TABLE 4. P values of differences between subgroups in decrease of ankle-brachial index (ABI) and pulsatility index (PI) for 22 patientsCharacteristicSexFollow-up after EBRTAgeFMYesNo>5 y<5 y<50 y>50 yNo. of patients1111184148139ABI.619.241.024.963––––PI femoral decrease.619.907.024.963––––PI popliteal decrease.269.937.221.414––––EBRT, external-beam radiotherapy.TABLE 5.Differences in decreases in measurements according to length of follow-upDecrease in perfused legFollow-up, n (%)P value>5 y (n = 14)<5 y (n = 8)ABI13 (93%)4 (50%).024PI femoral13 (93%)4 (50%).024PI popliteal12 (100%)a7 (88%).221ABI, ankle-brachial index; PI, pulsatility index.a n = 12; data for two patients were not available.
Venous Vascular Disease
Many patients had some symptoms of venous insufficiency, such as lower limb pain, feelings of heaviness and discomfort, night palsies, paresthesia, and edema. One patient (3%) wore compression stockings because of superficial vena saphena magna insufficiency, and one patient (3%) had unilateral superficial varicosis in the treated leg. Another three patients (9%) showed uni- or bilateral deep insufficient venous vasculature by duplex ultrasonography, which in all cases was located at the level of resection. One DVT (3%) and one partial venous obstruction (3%) were found, both at the resection level. Venous vascular obstruction was not seen at the level of cannulation.
DISCUSSION
ILP with TNF-α and melphalan, with or without adjuvant EBRT, has become an approved treatment strategy for locally advanced STS of the extremities after the publication of the results of an European multicenter trial performed in the 1990s.4 Because our center was one of the first to use this treatment modality, we now have had more than 10 years’ experience of ILP used to treat STS. This gives us the opportunity to evaluate the long-term treatment-related morbidity. Critical leg ischemia approximately 10 years after ILP, necessitating amputation in two patients, led to an interest of analyzing the vascular complications of ILP with or without EBRT.5
Despite a complete destruction of tumor vasculature, ILP does not seem to have any effect on the macrovasculature of the perfused limb.7,19,20 However, because atherosclerosis risk factors and chemotherapy could play a synergistic role in the progression of arterial stenosis, patients who already have severe atherosclerotic disease are less suitable for ILP.11,19,20
In our study, many patients had one or more risk factors for atherosclerosis. In the study population, there seemed to be more patients with diabetes or hypercholesterolemia than in the standard Dutch population. The smoking rate is similar (28% vs. 30%); however, another 31% used to smoke (Table 2).
Acute vascular complications after ILP have been described in the literature. Deep-vein thrombosis (DVT) occurs in 1.7% to 10% of cases in the immediate postoperative period.10 In our studies, three patients (7.7%) had a successfully treated DVT after ILP. DVT seems to be extremely difficult to diagnose because the postoperative effects of ILP itself—a warm, swollen edematous limb—mask the classical symptoms. To prevent this undesired complication, anticoagulant therapy is recommended. Thrombosis at the arteriotomy site has also been mentioned in earlier studies. It was not encountered in this study but should be treated by prompt trombectomy.9,21 In case of repeated ILP in the same limb, perfusion through more proximal arterial and venous sites is recommended because fibrosis at the previous operative site does not allow insertion of the cannulas at the same level. All patients in this study underwent only one ILP.
Long-term effects after ILP are mainly functional and consist of edema, stiffness, functional impairment, and muscle atrophy.21–23 Late vascular morbidity after ILP without EBRT has not been previously mentioned in other studies. In our study, one partial arterial occlusion (3%) was found. In contrast, long-term effects of EBRT have extensively been described in the literature. In a study of Butler et al.,12 three types of vascular damage have been described. At first, thrombosis occurs within 5 years after EBRT; a second fibrotic occlusion is seen within 10 years; and finally, a predisposition to the development of atheroma together with periarterial fibrosis is associated with a latent interval of 20 or more years. Rijbroek et al.24 mention claudication after a latent period. This is masked by the other effects such as pain, functional impairment, and edema. According to Kalman et al.,13 long-term vascular side effects of EBRT resemble the natural process of atherosclerosis, which is a combination of direct damage, periarterial fibrosis, and occlusion of vasa vasorum. The EBRT accelerates this process, sometimes 10 to 27 years after treatment. Little is known about the combined effects of ILP and EBRT. Vrouenraets et al.22 described one brachial arterial occlusion, but this was only 4 months after treatment. Olieman et al.16 described the occurrence of necrosis after ILP but did not find any increased tumor-related morbidity after ILP followed by EBRT. In another series, ILP was performed after EBRT, but it did not lead to more local toxicity or complications.25
In our study, amputation was performed in nine patients (23%). This is higher than the 9% to 21% described in the literature.4,26,27 However, amputations due to long-term complications like critical leg ischemia, which was performed in two patients (5.1%), have not been described in other studies. Furthermore, three complete (9%) and one partial (3%) arterial occlusion were found after the combined procedure.
Fortunately, these patients did not have invalidating symptoms of arterial occlusive disease. In most cases, vascular pressure measurements and duplex ultrasonographic evaluation showed statistically lower values compared with the contralateral extremity, but these were still within the normal range. This could explain the absence of symptoms.
The PI value normally increases progressively from aorta to ankle. A decrease in PI indicates stenosis in a more proximal vascular segment.28 In our study, six of seven patients with an abnormal femoral PI underwent iliac perfusion. This implies a vascular reaction at the level of cannulation. Furthermore, seven patients showed a decrease in popliteal PI compared with the femoral PI, which implies that vascular damage is present at a more proximal (i.e., cannulation or resection) level. However, with the present data, it is not possible to support this thesis because of the relatively small study population, and the absence of symptoms and other abnormal outcomes of the vascular work-up.
It is important to realize that blood vessels lose their elasticity with the years and are subject to the normal process of atherosclerosis. Furthermore, unilateral peripheral arterial occlusive disease is common. However, the fact that lower rates of ABI and PI were found in the treated leg in almost all patients and that no marked difference was found between younger and older patients makes the assumption of treatment-induced differences plausible.
Because only four patients with a lower leg STS were not treated with adjuvant EBRT, there are still no clinically relevant data about the late vascular damage of the single procedure of ILP. Thijssens et al.29 showed that adjuvant EBRT seems beneficial in all patients, so it might be impossible to evaluate the sole effects of ILP on the vascular system in the future.
Major late vascular complications after the combined procedure, like critical leg ischemia necessitating amputation, were found in two patients in this study. One patient had no risk factors for peripheral arterial occlusive disease besides smoking. He had had intermittent claudication 8 years after ILP and EBRT, and a normal ABI of 1.09. His condition did not improve after 2 years of conservative therapy and reconstruction was impossible, so he underwent an amputation 125 months after the initial limb salvage treatment strategy. The second patient, who had diabetes mellitus and familial cardiovascular disease, experienced no complications the first few years after ILP and EBRT. After 6 years, she experienced a pathological proximal tibia fracture due to radiation-induced osteonecrosis in the previous surgically treated area and needed to wear a brace. She lived for 3 years with a disabling function impairment of the knee and then developed signs of critical leg ischemia. An upper leg amputation was performed 110 months after the initial treatment. She now walks with a well-functioning prothesis.
The importance of leg preservation has been mentioned before. Even though most patients still are satisfied with the initial limb-saving treatment that they underwent, amputations due to major late complications with severe morbidity make the rationale of limb salvage worth reconsidering.
Recently, one patient was successfully treated with thrombectomy for an acute popliteal artery occlusion. This patient, who underwent an ILP at femoral level followed by EBRT for a STS in the fossa poplitea 5 years before, had no complaints of peripheral arterial occlusive disease during his vascular work-up for this study 10 months earlier. ABI (1.03) and femoral PI (6.3) were normal; popliteal PI was low (5.3). With duplex ultrasonography, some atherosclerosis in the femoropopliteal section was seen. This patient has diabetes and hypertension, is obese (body mass index >30), and was a former smoker, so he was especially at risk for developing atherosclerosis.
This study shows that despite the importance of preventing major late vascular complications after the combined procedure of ILP and EBRT, a routine noninvasive vascular work-up does not seem to add value to normal follow-up. It is more important to realize that patients after the limb salvage treatment strategy of ILP, followed by delayed tumor resection and EBRT, are at risk for late vascular complications. This risk is substantially raised when personal risk factors such as smoking, diabetes, hypertension, obesity, and hypercholesterolemia are present. Because symptoms of vascular complications can be masked by the normal effects of the treatment itself, the possibility of vascular morbidity should be considered if the patient has any complaint. Furthermore, all patients must be convinced of the importance of reducing their additional personal risk factors for atherosclerosis.
In conclusion, objective measurements show a time-related decrease (>5 years’ follow-up) of ABI and femoral PI in the treated leg, usually without subjective complaints. ILP followed by delayed resection and EBRT for a locally advanced STS can lead to major late vascular morbidity that requires amputation.

vascular perfusion sarcoma complications radiation


Effects of Ambulant Myofeedback Training and Ergonomic Counselling in Female Computer Workers with Work-Related Neck-Shoulder Complaints: A Randomized Controlled Trial

Objective: To investigate the effects of ambulant myofeedback training including ergonomic counselling (Mfb) and ergonomic counselling alone (EC), on work-related neck-shoulder pain and disability. Methods: Seventy-nine female computer workers reporting neck-shoulder complaints were randomly assigned to Mfb or EC and received four weeks of intervention. Pain intensity in neck, shoulders, and upper back, and pain disability, were measured at baseline, immediately after intervention, and at three and six months follow-up. Results: Pain intensity and disability had significantly decreased immediately after four weeks Mfb or EC, and the effects remained at follow up. No differences were observed between the Mfb and EC group for outcome and subjects in both intervention groups showed comparable chances for improvement in pain intensity and disability. Conclusions: Pain intensity and disability significantly reduced after both interventions and this effect remained at follow-up. No differences were observed between the two intervention groups.
Introduction
Work-related musculoskeletal complaints in the upper extremity are common among workers in Western industrialised countries. In the Netherlands, about 15% of the working population report complaints in the neck, shoulders and arms [1] defined as pain, numbness, or tingling, resulting in loss of productivity, sick-leave or even disability. In 1998, about 8% of all Dutch employees were absent from work due to work-related musculoskeletal complaints, and 2% of the employee population was absent from work for more than four weeks [2]. These complaints impose a substantial economic burden in compensation costs, lost wages, and productivity. Apart from the individual suffering, the financial costs within member states of the European Union associated with musculoskeletal complaints are high [3].
Work-related musculoskeletal complaints are multifactorial in origin and involve biomechanical, psychosocial, and individual components [4–6]. As a consequence different intervention approaches exist. Most often interventions address alterations of the physical work environment by adjustments of the work station and/or education about working posture according to ergonomic principles [7–10]. There are several studies reporting on the effectiveness of ergonomic approaches [11, 12] and it is commonly accepted that properly designed work stations are prerequisites for healthy working. However, in spite of attention to ergonomics musculoskeletal complaints remain a considerable problem [13–15] and this is the rationale for the search for innovative interventions.
A relatively new intervention approach addressing neck-shoulder complaints is myofeedback training based on the Cinderella-hypothesis [16]. The Cinderella-hypothesis is one of the most influential hypotheses explaining the process of development and persistence of pain in low intensity jobs [17] like computer work, and states that lack of sufficient muscle relaxation is a crucial factor in this process. Continuous muscle activity, even at low intensity levels, may result in homeostatic disturbances of the activated motor units due to affected blood flow and removal of metabolites [17]. Several studies have found an association between absence of moments of complete muscle rest and myalgia, especially for the commonly affected descending part of the trapezius muscle (e.g. [18–20]). Warning subjects when their muscle relaxation is insufficient could thus contribute to recovery, and this is the rationale for the Cinderella-based myofeedback training. This approach is different from traditional myofeedback training in which feedback is provided when muscle activity exceeds a certain level thereby aiming at decreasing muscle activation (e.g. [21, 22]). As the Cinderella-hypothesis suggests however that muscle relaxation is more relevant than muscle activation, a myofeedback-based intervention aiming at increasing muscle relaxation may be more beneficial.
The Cinderella-based myofeedback system [23] consists of a harness incorporating dry surface electrodes and a feedback unit. The system is ambulant and subjects can wear the harness under their clothes during working days. The harness is connected to a feedback unit worn at the waist which provides feedback by means of vibration and a soft sound when muscle relaxation is insufficient. A feasibility study using this equipment for four weeks in a group reporting work-related neck-shoulder complaints resulted in significantly decreased levels of pain intensity and also changed muscle activation patterns. These effects were still at hand four weeks after the myofeedback training ended [23]. However, as the study did not contain a control group and only investigated the lasting effects of the intervention for a short follow-up period (4 weeks), further research is needed.
As proper ergonomics are indispensable for healthy working, the myofeedback training is preferably applied in combination with an intervention approach aimed at improving ergonomics. Thus, the present study aimed at investigating the immediate and lasting effects of Cinderella-based myofeedback training including ergonomic counselling, compared to ergonomic counselling alone, on pain intensity and disability in females with work-related neck-shoulder complaints. As interventions focusing on multiple factors have shown to be related to decreased incidence of complaints [24] it was hypothesised that 4-weeks myofeedback training including ergonomic counselling would be more effective in reducing pain intensity and disability than the intervention based on ergonomic counselling alone.
Methods and materials
Design and subjects
A randomized controlled trial was performed to assess the effect of 4-weeks Cinderella-based myofeedback training combined with ergonomic counselling (together referred to as Mfb), compared to ergonomic counselling alone (EC), on pain intensity and disability. Measurements were performed prior to intervention but before randomisation (Baseline), immediately after four weeks of intervention (T0), and at three (T3) and six (T6) months after the intervention.
Participants were recruited in Sweden (area of Göteborg) and the Netherlands (area of Enschede) between March 2003 and June 2005. Computer workers like job counselors (Sweden) and (medical) secretaries (Sweden and the Netherlands) were approached by telephone and announcements, and volunteers were subsequently sent a screening questionnaire [25] which was developed within the EU-funded NEW project (Neuromuscular assessment in the Elderly Worker) [26]. Subjects eligible for participation were symptomatic female computer workers, predominantly over the age of 45 as the prevalence of complaints is especially high in this age category [27], working for at least 20 hours a week, and reporting perpetuating work-related musculoskeletal complaints in the neck and/or shoulder region for at least 30 days during the last year.
Subjects were excluded when they reported pain in more than 3 body regions, when they suffered from severe arthrosis or joint disorders, when they were using muscle relaxants, or when reporting other complaints in the upper extremity not related to (computer) work.
Power calculation, based on the results of Hermens and Hutten [23], indicated that at least 35 subjects should be included in each intervention group (estimated proportion of subjects showing an effect on pain intensity was set at 0.6 in the Mfb group and 0.2 in the EC group; 1−β = 0.90; α = .05). Block randomization was used to assign subjects to either Mfb or EC: When a new group of subjects started the intervention, half of them were assigned to Mfb and half of them were assigned to EC. The study was approved by the local Medical Ethics Committees and all participants gave their informed consent prior to participation.
Interventions
The interventions were provided by three different therapists: One physiotherapist in Sweden and two health scientists in the Netherlands. They were thoroughly trained and practiced together prior to the start of the study to ensure that they would provide as identical interventions as possible. The character of the intervention made blinding of the therapists and the subjects to the intervention impractical. To prevent from information bias, subjects were informed that the aim of the current study was to compare the effects of two interventions and that there was no evidence favouring one of these interventions.
Ergonomic counselling (EC)
Subjects received four weeks of intervention during which they kept a diary of activities and pain intensity scores. During the four weeks period they were visited weekly by their therapist. The first visit comprised an ergonomic workplace investigation by means of the risk inventory of Huppes et al. [28]. This checklist contains questions to evaluate work tasks, working hours, work load, work station, and working methods. Based on the outcome, possible improvements were discussed with the subject. With regard to the work station, the focus was primarily on modifying the existing work station rather than providing new equipment. The remaining visits were used to further discuss the ergonomic aspects, the consequences of possible ergonomic adjustments etc., according to a manual to guarantee a uniform intervention.
Myofeedback (Mfb)
Subjects randomized to the Mfb group received Cinderella-based myofeedback training on top of EC. A two-channel ambulant myofeedback system combined with a harness incorporating dry surface Electromyography (sEMG) electrodes to enable a stable recording of upper trapezius muscle activity was used. The harness was connected to a sEMG processing and storage device (see Picture 1).
Picture 1
Myofeedback system: Harness and processing/storage unit
The sEMG signal was amplified (15×), band pass filtered between 30 and 250 Hz, sampled at 512 Hz, digitized (22 bits ADC), and smooth rectified with removal of the low frequency components. Embedded software provided the detection and calculation of muscle rest, expressed as the sEMG parameter Relative Rest Time, which was defined as the percentage of time in which Root Mean Square was below a threshold (10 μV) for at least 0.12 s. This threshold was based on the noise level of the myofeedback system including mounted electrodes at the skin. Sensory feedback by means of vibration and a soft sound was provided after each 10 s interval when the relative duration of muscle relaxation in that particular interval was below 20%. The choice for a 10 s interval was based on the results of Voerman et al. [29], and the 20% threshold was chosen based on the work of Hägg and Åström [30]. Subjects were instructed that they should respond to the feedback by relaxation, which could be reached by slightly depressing the shoulders, or by sitting down quietly with the eyes closed, the hands in the lap while breathing deeply. Another relaxation strategy subjects were instructed was to maximally elevate the shoulders for three seconds to build up muscle tension and then to let loose this tension. This relaxation was anticipated to contribute to recovery of the Cinderella motor units. When there was no adequate response to the feedback, i.e. relaxation, the duration of the feedback signal progressively increased.
Immediately after Baseline, subjects assigned to the Mfb group were given the myofeedback device and they were explained the working mechanism and background of the myofeedback training. Subjects wore the system for four weeks, for at least eight hours a week (distributed over two hours a day and two days a week as a minimum) while performing their regular work. During the weekly visits the sEMG-data from last week were scrutinized and discussed to give the subject insight in their relaxation patterns and to identify possible situations of concern. This procedure was facilitated by means of the diary.
Assessment of pain intensity and disability
Pain intensity in the neck, shoulder (left and right), and upper back at time of the measurement was assessed by means of four Visual Analogue Scales [31]. Subjects were instructed to rate their subjectively experienced level of pain intensity at that moment for each body region. The Visual Analogue Scale consists of a 10 cm horizontal line with ‘no discomfort at all' at the left and ‘as much discomfort as possible' at the right endpoints of the line. Psychometric properties of the Visual Analogue Scale have been shown to be sufficient [32–34].
The level of subjectively experienced disability was assessed with the Pain Disability Index, a self-rating scale that measures the impact of pain on the abilities to participate in life activities [35]. The Pain Disability Index contains 7 items, one for each domain, i.e. (1) family and home responsibilities, (2) recreation (hobbies, sports, and leisure time activities), (3) social activity (participation with friends and acquaintances), (4) occupation (activities partly or directly related to working), (5) sexual behavior (frequency and quality of sex life), (6) self care (personal maintenance and independent daily living), and (7) life-support activity (basic life-supporting behaviors). Answers were provided on a categorical 11-points scale with ‘not disabled’ and ‘fully disabled’ at the extremes. In a chronic pain population, psychometric properties of the Pain Disability Index appeared to be sufficient [36].
Analysis
Data inspection showed non-normal distributions for all of the variables, and data were therefore log transformed, enabling parametric analyses. Analyses were performed both on the group as well as the individual level.
For each subject, VAS scores for the neck, left shoulder, right shoulder, and upper back were summed and averaged resulting in a combined neck-shoulder pain intensity score. Differences between the two interventions, i.e. Mfb and EC, for VAS and the Pain Disability Index were investigated using a linear mixed-model analysis technique for repeated measurements. The following variables were included in the model as fixed factors: Time of measurement (i.e. Baseline, T0, T3, and T6), intervention type (i.e. Mfb and EC), and study group (i.e. Sweden and the Netherlands), including two-way interactions. The factor study group comprises variance due to possible (socio)demographic differences as well as variance caused by the different therapists, organizations, and job characteristics in the two countries. The factor subject was included in the model as a random factor. Paired and independent samples t-tests were used for Post Hoc analysis.
At the individual level the percentages of subjects improving and the odds for improvement in both intervention groups were investigated. First, individual differences were calculated between Baseline and T0, Baseline and T3, and Baseline and T6 for pain intensity in the neck-shoulder region (i.e. the averaged score on the VAS for neck, left and right shoulders, and upper back) and Pain Disability Index. These differences were then dichotomized into ‘clinically relevant improvement’ or ‘equal/deteriorated.’ For the Visual Analogue Scale the cut-off point for a clinically relevant improvement was defined at 13 mm which corresponds to the upper limit of the confidence interval of clinically relevant changes in Visual Analogue Scale scores in acute and non-acute pain patients as reported by Kelly in 2001 [37]. This cut-off point was also the result of the study of Todd [34]. Cut-off points for clinically significant changes in the Pain Disability Index scores have not been provided in literature. For a comparable measure, the Neck Disability Index which is a 10 items scale with 6 answering options resulting in scores varying from 0 to 50, the cut-off point was set at 5 which is 10% of the maximum score [38]. Using this as a starting point, a clinically relevant change was defined as a change of ≥10% of the maximum score of 70 of the Pain Disability Index, i.e. ≥7 units of the Pain Disability Index score.
Logistic regression analyses providing Odds Ratios were performed to investigate whether the two intervention groups differed in terms of chances for clinically relevant improvements in pain intensity and disability. Three different models were investigated: Model I represents the crude Odds Ratio describing only the relationship between intervention type and odds for improvement without adjustment for confounding factors. The factors study group and baseline pain intensity/baseline disability were assumed potentially confounding factors. To correct for these factors, two additional models were built as extensions of Model I: Model II incorporates study group as confounding factor, and Model III is an extension of Model II incorporating also the factor baseline pain intensity/baseline disability level. For Models II and III interaction effects were additionally included in the analysis, to study effect modification, but these remained only included when significant. −2 Log Likelihood tests were used to select the best model. Odds Ratios including 95% Confidence Intervals were calculated and presented for each of the models.
Statistical Package for Social Sciences 11.5 was used for statistical testing and alpha was set at .05 for statistical significance.
Results
Subjects
Seventy-nine female computer workers with neck-shoulder complaints were included in this study: Forty-two subjects were assigned to the Mfb group and 37 to the EC group. Mean age was 52.0 (SD 5.8 years) in the Mfb group and 50.7 (SD 5.5) years in the EC group. Mean duration (days between Baseline and T0) of the interventions was 37 (SD 8) days for the Mfb group and 36 (SD 7) days for the EC group. Forty-one out of the 79 subjects were recruited in Sweden and the remaining 38 in the Netherlands. The number of subjects at Baseline, T0, T3, and T6 and the number of drop-outs are shown in Diagram 1.
Diagram 1Flow chart subject recruitment and randomisation
Drop-outs did not differ in age, weight, height, BMI, and pain intensity scores (Visual Analogue Scale), and disability (Pain Disability Index) from those fulfilling the intervention (p > .08).
Table 1 provides an overview of sociodemographic characteristics of the subjects in the Mfb and EC groups. Thirty-eight subjects reported complaints in both the neck and shoulder, while 41 subjects reported complaints either in the neck or in the shoulder at the time of recruitment. Comparison of the characteristics between the Mfb and EC groups indicated that subjects assigned to the Mfb group reported more years within the same job compared to the EC group (p < .05).Table 1Characteristics of subject populationMfb (n = 42)EC (n = 37)Sociodemographics Body mass index25.2 (3.9)25.2 (3.7) Side dominance% Right-handed95%97% Living situation% Living alone16.710.8 Working hours per week32.8 (7.8)32.8 (8.3) Working hours per week since (in years)17.0 (11.4)*12.0 (8.9)*Complaints Trouble in neck last yearYes92.991.9 Trouble shoulders last yearYes, in both shoulders36.632.4Yes, in the right shoulder36.643.2Yes, in the left shoulder12.213.5 Trouble in upper back last yearYes66.748.6 Was work performance affectedYes31.718.9*Significant at the .05 level.
Analysis at group level
Pain intensity
Baseline (geometric) mean VAS scores for each region separately were 27 mm (neck), 15 mm (left shoulder), 14 mm (right shoulder), and 13 mm (upper back) in the Mfb group and 24, 14, 19, and 18 mm in the EC group respectively.
Figure 1 shows a box plot of the VAS score in the neck-shoulder region at Baseline, T0, T3, and T6 for the Mfb and the EC group. A clear decrease was observed at T0, T3, and T6 compared to Baseline, although at T6 pain intensity seemed to increase slightly in both groups.Fig. 1Box plot for averaged VAS score of pain intensity in the neck-shoulder region at Baseline, T0, T3, and T6 for both the Mfb and the EC group
Mixed linear modelling showed that pain intensity in the neck-shoulder region significantly changed over time (F = 12.08, p ≤ .01), without additional effects for the type of the intervention (F = 1.54, p = 0.22), study group (F = .48, p = .49), or interaction effects (F ≤ .87, p ≥ .35). Post Hoc comparisons revealed that the VAS score was significantly reduced at T0 (t = 4.37, p < .01), T3 (t = 5.10, p < .01), and T6 (t = 3.54, p < .01) compared to Baseline but also the reduction between T0 and T3 was significant (t = 2.85, p = .01).
Disability
Figure 2 shows a box plot of the Pain Disability Index score at Baseline, T0, T3, and T6 for the Mfb and the EC group. A comparable pattern to what was observed for pain intensity was found, with decreased disability levels at T0, T3, and T6 compared to Baseline.Fig. 2Box plot for the Pain Disability Index score at Baseline, T0, T3, and T6 for both the Mfb and the EC group
Disability levels significantly changed over time (F = 17.68, p < .01) and were significantly different between the two study groups (i.e. Sweden and the Netherlands) (F = 5.30, p = .02). No additional effects were found for intervention type (F = .86, p = .35) nor the interaction terms (F ≤ 1.97, p ≥ .12). Post Hoc comparisons showed that subjects in the Swedish study group had lower Baseline values and reported reductions in disability only between Baseline and T0 (t = 2.20, p = .04) with a trend for reductions at T3 (t = 1.89, p = .07) and T6 (t = 1.81, p = .08). Subjects in the Dutch study group showed a significant decrease at T0 (t = 3.26, p < .01), T3 (t = 3.58, p < .01), and T6 (t = 3.51, p < .01) compared to Baseline.
Analysis at the individual level
Pain intensity
Figure 3 gives an overview of the percentage of subjects in the Mfb and EC groups showing an improvement in pain intensity in the neck-shoulder region. About half of the subjects showed a clinically relevant improvement in pain intensity in the neck-shoulder region. Slightly more subjects in the Mfb group showed improvements compared to the subjects in the EC group immediately after the intervention period (T0) and at 6 months follow-up (T6).Fig. 3Percentage of subjects showing improvements in averaged VAS score of pain intensity in the neck-shoulder region at T0, T3, and T6 compared to Baseline for the Mfb and EC group [without correcting for confounding factors]
Crude Odds Ratios (Model I) for improvement showed higher odds for clinically relevant improvement in the Mfb group at T0 and T6 compared to Baseline, while between T3 and Baseline subjects assigned to EC were more likely to show improvements (see Table 2). However, Odds Ratios were not significant (p ≥ .36) also not when corrected for potential confounding factors (p > .19). −2 Log Likelihood tests indicated that Model III, adjusting for the factors study group and baseline pain intensity/disability level, superimposed the Models I and II (−2 LL; p < .05). As no significant interaction effects were found (p > .08) these were excluded from the final models as presented in Table 2.Table 2(Adjusted) odds ratios (95% confidence interval) for improvement in pain intensity in the neck-shoulder region for the Mfb group compared to the EC groupModel IModel IIModel IIIVAS1.561.593.42Baseline–T0(.60–4.05)(.71–4.14)(.55–21.11)VAS.78.78.40Baseline–T3(.29–2.08)(.29–2.09)(.08–1.99)VAS1.311.311.04Baseline–T6(.47–3.60)(.47–3.64)(.29–3.77)Model I: Odds Ratio Crude.Model II: Odds Ratio Adjusted for factor study group.Model III: Odds Ratio Adjusted for factor study group and VAS at Baseline.
Disability
An overview of the percentage of subjects in the Mfb and EC groups showing an improvement in disability is provided in Fig. 4.Fig. 4Percentage of subjects showing clinically relevant improvements in Pain Disability Index at T0, T3, and T6 compared to Baseline for the Mfb and EC group [without correcting for confounding factors]
Immediately after the intervention period about twice as many of the subjects in the Mfb group showed clinically relevant improvements in disability compared to the EC group. This share of subjects increased somewhat in both groups after three months and then showed a small decline after six months where about one third of the subjects of the EC group and half of the Mfb group showed clinically relevant improvements in disability.
Subjects assigned to the Mfb group had higher odds for improvement in disability at T0, T3, and T6: At T3, the odds for improvement in disability was 2.77 times higher in the Mfb group compared to the EC group which was significant (Model I; 95% CI 1.00–7.65; p = .05). When corrected for confounding variables, however, Odds Ratios for improvement were still higher for the Mfb group compared to the EC group, but this was not significant (p ≥ .057) except for Model II for changes between Baseline and T3 (p = .04). Baseline disability levels significantly affected Odds Ratios: Model III was generally better than the models I and II (−2 LL; p < .05). As no significant interaction effects were found (p > .08) these were excluded from the final models as presented in Table 3.Table 3(Adjusted) odds ratios (95% confidence interval) for improvement in disability the Mfb group compared to the EC groupModel IModel IIModel IIIPain disability index2.702.721.48Baseline–T0(.97–7.54)†(.971–7.60)†(.39–5.62)Pain disability index2.772.991.64Baseline–T3(1.00–7.65)*(1.03–8.65)*(.34–7.97)Pain disability index2.542.611.48Baseline–T6(.88–6.82)†(.91–7.47)(.37–5.88)Model I: Odds Ratio Crude.Model II: Odds Ratio Adjusted for factor study group.Model III: Odds Ratio Adjusted for factor study group and Pain Disability Index at Baseline.*p ≤ .05.†.05 ≤ p ≤ .10.
Discussion
This randomised controlled trial investigated the effects of 4-weeks ambulant myofeedback training combined with ergonomic counselling in subjects with work-related neck-shoulder complaints relative to ergonomic counselling alone, on pain intensity and disability. The effects were evaluated immediately after the interventions, and at three and six months follow-up. Mean pain intensity and disability levels significantly reduced after both interventions (i.e. Mfb and EC). The effects were clinically relevant in a large part of the subjects: About 30–50% of the subjects showed clinically relevant improvements in pain intensity and/or disability. No difference was found for the effect of the intervention on outcome and after correction for confounding factors subjects in both intervention groups did not differ with regard to chances for clinically relevant improvements in pain intensity and disability.
Several studies have shown the beneficial effect of myofeedback training on pain reduction [21, 39–43] although Faucett and colleagues [22] reported changes in muscle activity rather than changes in pain intensity. The feedback approach used in these studies is different from the Cinderella-based myofeedback approach in that the traditional feedback method provides feedback when muscle activation is too high [21, 22, 42, 44–47], rather than when the time the muscle has relaxed is too short [23]. Two previous studies applying the Cinderella-based myofeedback training in subjects with work-related complaints [23] and subjects with a whiplash associated disorder [48] reported reduced pain intensity and disability levels. Compared to these studies, baseline pain intensity values were generally lower and the cut-off points for clinically relevant changes were set to higher levels in the current study, but the results indicate a comparable percentage of subjects reporting clinically significant reductions in pain intensity, i.e. between 35 and 50% of the subjects. This consistency in results adds to evidence for the effectiveness of (Cinderella-based) myofeedback training on pain intensity and disability in musculoskeletal neck-shoulder complaints.
In line with existing literature (e.g. [8, 10, 49, 50]) also subjects in the ergonomic counselling group reported reduced pain intensity and disability. It was however hypothesised that a treatment approach including both myofeedback training and ergonomic counselling (Mfb) would be more effective than treatment comprising only ergonomic counselling (EC) as interventions focusing on multiple factors have shown to be related to decreased incidence of complaints [24]. In the current study the two types of interventions did not differ in terms of outcome. This is in line with findings of other studies (e.g. [8, 10, 51–53]) that concluded that occupational interventions have generally comparable effects, although these studies did not include a myofeedback intervention. Newton-John and others [43] compared myofeedback with cognitive-behavioural therapy and a waiting list control group and found that both interventions showed favourable outcome in terms of pain intensity and disability compared to the waiting list control group without a difference between the two interventions.
There are possible explanations for the absence of differences between the two groups. One concerns the presence of subgroups in which the intervention is beneficial. Results showed that the effect is clinically relevant in about 30–50% of the subjects. Main question to be addressed here is whether, and how, these subjects can be characterised in terms of cognitive-behavioural characteristics and whether this characterisation can contribute to predict outcome of the intervention. This could substantially improve the efficiency and effectiveness of the interventions. Further, differences between the two groups may have been masked by using rather generic outcome measures. For instance, coping and patient-rated parameters may better represent the difference in outcome between different kinds of interventions [54]. Investigation into the specific working mechanisms of both interventions could clarify this. Finally, initial VAS and disability levels were low in both the Mfb and the EC group, especially in the study group from Sweden. This results in a smaller potential for improvement (floor effect) and as a result a smaller chance for finding differences between the Mfb and EC groups.
Methodological considerations
This study did not include a non-intervention or placebo control group (for instance randomly administered feedback) which makes it hard to control for non-specific effects like regression to the mean or the Hawthorne effect [55]. This effect was already described in 1933 by Mayo, and is reported as a significant positive effect without causal basis in the theoretical motivation for the intervention, but is related to the effect on the participants knowing themselves to be studied in connection with the outcomes measured. An argument against such effect is that although it might occur in connection with the intervention (i.e. at T0) it is not likely that this effect would remain [56] after three to six months. In addition, the study population also contained subjects with chronic complaints (i.e. duration >6 months) who received a variety of treatments in the past, which were not successful. It is likely to expect that any non-specific effects of treatment would already have occurred during past treatments and that this effect in the current study would thus be small. Furthermore, results from previous studies learned that pain reduction in myofeedback-trained subjects were higher compared to a wait-list control group [43], a no intervention group [46], or subjects receiving a placebo [57]. Furthermore, an attention-only group showed no changed outcome in terms of disability and pain intensity [58].
The present study included a rather specific subject population: Participants were females, predominantly over the age of 45, still at work, and characterised by relatively low pain intensity and disability levels. Interpretation and extrapolation of results to other populations therefore requires caution, but as comparable effects of Cinderella-based myofeedback training have also been shown in mixed, younger subject populations [23, 48] and in a sample of patients who were on sick leave because of their neck-shoulder complaints [48], generalisation of findings might be legitimate. The subjects were selected based on self-reported complaints rather than a clinical evaluation. In a previous study [60] with female computer users above the age of 45, applying the same inclusion criteria as the present study, it was found that in subjects with neck-shoulder complaints the following clinical diagnoses were most prevalent: Trapezius myalgia (38%), tension neck syndrome (17%), and cervicalgia (17%). These diagnoses were found in 60% of the subjects reporting complaints. There were cases with supraspinatus tendinitis, frozen shoulder, and biceps tendinitis, but these were less common. This general pattern of clinical signs is likely to be at hand also in the present study. It could be hypothesised that myofeedback may be particularly relevant and helpful in cases with muscular pain syndromes.
Despite extensive standardisations, the recruitment of subjects in two different study groups (Sweden and the Netherlands) resulted in heterogeneity of the subject population with regard to age, working hours, seniority, and working posture. To correct for this, the factor study group was considered a confounder needed to control for during analysis. This reduced the power of the study. An additional likely confounding factor is the compliance of the patient and therapist to the intervention. This is an often uncontrolled and thus potentially confounding factor in occupational intervention studies [59] and it is known that changes in knowledge and skills do not necessarily result in a behavioural change. In the Mfb group, the compliance was partly controlled as the number of hours the system was worn was recorded by the system itself, but the compliance to ergonomic knowledge and skills is hard to register objectively. This definitely is a challenge in future occupational intervention studies.
The drop-out rate in the Mfb group was higher than in the EC group (i.e. nine compared to five), which was probably related to the myofeedback system itself. Some subjects found the system inconvenient and disturbing in daily working activities. This may have suppressed the effect of the intervention. Improvement of the current device in terms of usability is therefore required to optimise the myofeedback training.
Conclusions
Four-weeks of intervention significantly reduced pain intensity and disability, and this effect remained after three and six months follow-up. Myofeedback training combined with ergonomic counselling is thus beneficial for female computer workers over the age of 45, reporting pain and disability in the neck-shoulder region but no evidence was found favouring myofeedback training combined with ergonomic counselling over ergonomic counselling alone. Future research may aim at identifying possible subgroups of patients in which the interventions are especially beneficial. This may enhance the efficiency and the effectiveness of the interventions. Finally, as non-specific effects may have interfered with outcome, future studies could include a placebo control group for more insight in the specific effects of ambulant myofeedback training combined with ergonomic counselling.

myofeedback training
work-related neck-shoulder complaints
neck-shoulder region