Extracorporeal shock wave therapy to treat neurogenic heterotopic ossification in a patient with spinal cord injury: A case report

Abstract

Objective: To evaluate the efficacy and safety of treatment for neurogenic heterotopic ossification (NHO) using extracorporeal shock wave therapy (ESWT) in persons with spinal cord injury (SCI).

Design: Single case report.

Setting: Department of Physical Medicine and Rehabilitation, Veterans Health Service Medical Center.

Participants: A 55-year-old male with cervical SCI, who developed painful NHO around the right hip joint.

Interventions: Ultrasound-guided ESWT that used 4,000 shocks at the rate of 3 Hz and the energy flux density between 0.056 and 0.068 mJ/mm² was applied to the NHO region a total of 7 times, weekly.

Outcome Measures: We assessed the treatment outcomes using a visual analog scale (VAS) score, wheelchair sitting time and size of NHO.

Result: After 7 weeks of ESWT treatment, his pain reduced from a VAS score of 7–8 to 3 and his wheelchair sitting time increased. However, there was no significant change of size of NHO.

Conclusion: The application of ESWT could be a possible alternative to other treatments for NHO in persons with SCI.

Clinical Trial Registry Number: 2019-03-003.

Introduction

Neurogenic heterotopic ossification (NHO) is a pathological ectopic bone formation that gradually develops in soft tissues, in relation to central nerve system.^1–3 The incidence of NHO in persons with spinal cord injury (SCI) is as high as 20%.⁴ Treatment of NHO is important because NHO can cause disabilities such as pain and joint contracture, and it can also lower activities of daily living (ADLs).²

Extracorporeal shock wave therapy (ESWT) is a treatment using a short, intense, energy waves that are faster than the speed of sound.⁵ The basic concept of ESWT is similar to lithotripsy which has been used since the 1980s; using acoustic shockwaves for breaking kidney stones without surgery.^5,6 Recently, ESWT has been used to treat musculoskeletal disorders because it has effects such as neovascularization, anti-inflammatory action, tissue regeneration effect, anti-apoptosis and chondroprotective effect.^7–12 ESWT treatment for the musculoskeletal disorder has been reported no serious side effects, while mild and short lasting side effects such as tingling, aching, redness or bruising have been rarely reported.¹³ There have been a few studies regarding ESWT treatment for NHO, however, no study has been reported on ESWT treatment for SCI persons.^14–16

In this study, we describe a case of a tetraplegic SCI with chronic painful NHO who was subsequently treated using ESWT with favorable outcomes.

Case report

A 55-year-old male diagnosed as having a complete C4 SCI[S(C5/C5)] according to American Spinal Injury Association (ASIA) Impairment Scale A visited the department of physical medicine and rehabilitation on September 20, 2017 due to severe right hip pain. The subject sustained tetraplegia in a fall while he was in the military in July 1983, for which a C5/6 vertebral body fusion was performed at that time. As time passed, the subject also developed cervical spinal stenosis at multiple levels with cervical myelopathy at the C3/4 level. Magnetic resonance imaging showed severe central stenosis and compressive myelopathy at C3/4 with vertebral body fusion at C5/6 and a cystic lesion in the spinal cord at this level. The results for manual muscle testing of both shoulder flexors and extensors were poor, and the others were all zero. Sensory examination revealed hypoesthesia in all extremities, and the modified Ashworth scales for all joints were grade 0. Moreover, no definite limitation of motion except plantar flexion of the left ankle was noted. The initial modified Barthel index and Spinal Cord Independence Measure score of the subject were 26 and 35, respectively.

At the initial visit to the department of physical medicine and rehabilitation, the subject had suffered from severe right hip pain with a visual analog scale (VAS) score between 7 and 8 without definite heatness or swelling (Table 1). A radiograph of the right hip revealed NHO on the greater trochanter of the right hip (Fig. 1A). The maximum length of long axis for the NHO according to the radiograph was 13.63 mm and the maximum length of short axis for the NHO was 8.13 mm. The Computed Tomography (CT) scans also showed NHO on the greater trochanter of the right hip (Fig. 2). The NHO volume was measured using 3D slicer 4.10 and was found to be 818 mm³. The serum alkaline phosphatase level was 192 IU/L. Medications(aceclofenac 100 mg twice a day and disodium etidronate 600 mg once a day) and physical modalities for a minimum period of 3 weeks were used to treat the pain. However, he still complained of severe pain with a VAS of 7–8 after 3 weeks of conservative treatments (Table 1). In addition, because of his severe pain, the subject could not sit on the wheelchair for more than an hour and he could not transfer well.

Table 1. Measurements of clinical outcomes during the treatment period.

Clinical outcome	Initial visit, before conservative treatmentsa	Before ESWT, after 3 weeks of conservative treatments	After ESWT	6 months after ESWT
VAS score	7–8	7–8	3	3
Wheel chair sitting time (h)	less than 1 h	less than 1 h	more than 10 h	more than 10 h

Note: ESWT, extracorporeal shock wave therapy; VAS, visual analog scale.

^aConservative treatments are included non-steroidal anti-inflammatory drugs, bisphosphonates and physical modalities.

Figure 1.

Radiograph of the hip showed neurogenic heterotopic ossification before and after extracorporeal shock wave therapy treatment. (A) Radiograph of the hip before extracorporeal shock wave therapy treatment. (B) Radiograph of the hip after extracorporeal shock wave therapy treatment.

Figure 2.

Computed tomography of the hip showed neurogenic heterotopic ossification before extracorporeal shock wave therapy treatment. (A) Axial view of the hip. (B) Coronal view of the hip.

ESWT was applied using Dornier Aries AR2 (Dornier MedTech, Wessling, Germany) for the right hip NHO under ultrasound (Accuvix XQ; Medison, Seoul, Korea) guidance because conservative treatments were ineffective. Each application of ultrasound-guided ESWT used 4000 shocks at the rate of 3 Hz and the energy flux density (EFD) between 0.056 and 0.068 mJ/mm² (intensity 5∼6) and ESWT was administered 7 times each weekly. During the 7 weeks of the treatment period, the subject tolerated ESWT treatments, and no serious side effects were observed.

After 7 weeks of ESWT treatment, although the size of the NHO measured by radiograph was not definitely changed, his pain reduced to a VAS score of 3 (Table 1 and Fig. 1B). In addition, the subject could sit on the wheelchair for more than 10 h and felt better during mobility and transfer. These therapeutic effects of ESWT lasted for 6 months (Table 1).

Discussion

In this report, we have described the effect of ESWT on NHO in a person with SCI who had been previously treated with non-steroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, and physical modalities. Our report shows that ESWT can be used for treating NHO to reduce pain and improve ADLs.

Many treatments including medication such as NSAIDs and bisphosphonates, radiation, physical modalities and surgical excision have been used to treat NHO.^4,17–21 Among them, NSAIDs are frequently used as prophylaxis for NHO by inhibiting the osteogenic differentiation of progenitor cells; however, the long term use of NSAIDs can increase the risk of gastrointestinal distress.¹⁷ Bisphosphates are also used to inhibit calcification because of their anti-resorptive effects by increasing osteoclastic activity.^18,19 Few studies have asserted that these treatments are effective as a prophylaxis of NHO, especially if the medication is started earlier, the bone scan is suitable for NHO, and radiography is normal.^18,19 Radiation therapy also irradiates pluripotent mesenchymal cells that are related to the formation of NHO, and these treatments would be considered according to the individual subject’s situation such as cost and lower medication compliance.²⁰ Physical modalities also can be an option for treatment of NHO; however, some opinions differ regarding the treatment value of physical modalities.⁴ Surgical excision is also used for NHO, is recommended for the subjects who suffer from functional loss because of NHO.⁴ However, with surgery there is a risk of delayed wound healing, infection, nerve injury, and recurrence of NHO.²¹ Despite the widespread use of ESWT, there have been limited studies on the treatment effects of ESWT for NHO.^14–16 In 2005, Brissot et al.¹⁶ recruited 26 subjects who underwent ESWT weekly for 4 weeks (4000 shocks, 3 Hz and 0.54∼1.06 mJ/mm²), and they found that ESWT was effective for pain, increasing range of motion (ROM), and increasing walking distance.¹⁶ Moreover, 21 out of 26 subjects had non-neurogenic heterotopic ossification due to total hip arthroplasty, burns, spontaneous occurrence and trauma of lower extremities.¹⁶ The other five subjects had NHO due to head trauma and paraplegia which was not clearly interpreted about the detail vector; e.g. congenital condition, cerebral palsy, cauda quina syndrome, and so on.¹⁶ In 2013, Reznik et al.¹⁵ investigated a case report of the post-traumatic brain injury person who suffered from recurring NHO around the hip joint.¹⁵ For the treatment of NHO, ESWT was performed 4 times during 6 week period at an intensity level of 5–6, and a total of 3000 shocks were given at each treatment.¹⁵ They found that the use of ESWT reduced pain from the VAS score of 9 to 0, increased right hip ROM and increased step length, and these effects were maintained for 5 months.¹⁵ In 2015, Choi et al.¹⁴ reported the effects of ESWT for chronic painful NHO around the left hip joint after traumatic brain injury.¹⁴ ESWT was conducted weekly for 3 weeks, and each ESWT application included 4000 shocks at a rate of 3 Hz and 0.056–0.068 mJ/mm² of EFD.¹⁴ Their study showed that ESWT was effective in reducing pain from the initial VAS score of 8–10 to 3, improving left hip ROM, walking distance and sitting time in a wheelchair.¹⁴ In this case, the subject was treated with NSAIDs, bisphosphonates, and physical modalities for approximately 3 weeks; however, he still had severe right hip pain and decreased wheelchair sitting time. However, when he was treated with ESWT, his pain and ADLs, including sitting time improved and he could transfer comfortably. The authors assumed that the application of ESWT would be relatively safe, non-invasive, simple to perform and effective for treating NHO by reducing pain intensity and improving ADLs in persons with SCI.

Although the therapeutic mechanisms of ESWT have not been clearly established, some possible principle hypotheses may be as follows.^7–11 First, ESWT induces the ingrowth of neovascularization related to the release of angiogenesis markers, which could lead to anti-inflammatory effects.^7–9 In 2003, Wang et al.⁷ suggested that shock wave therapy produced neovascularization and markers associated with angiogenesis including proliferating cell nuclear antigens, vessel endothelial growth factor and endothelial nitric oxide (NO) synthase in rabbits.⁷ In the same year, Takahashi et al.⁸ also studied the mechanism of pain relief after application of shock wave therapy, and they asserted that these may result from decreased expression of calcitonin gene-related peptides which are well known as excitatory nociceptive transmitters in the dorsal root ganglions.⁸ In 2009, Mariotto et al.⁹ also demonstrated that ESWT can induce tissue proliferation by triggering anti-inflammatory action related to angiogenesis-related markers.⁹ In that study, the increased level of NO and the suppressed level of nuclear factor kappa B activation suggested clinically beneficial action on tissue inflammation.⁹ In addition, the mechanisms observed induced the hypoxic injured tissue to undergo aerobic metabolism.⁹ Second, ESWT might reduce chronic pain by reorganizing pathologic memory traces, and these can cause chronic pain relief.¹⁰ In 2008, Wess et al.¹⁰ asserted that chronic pain is associated with a pathologic reaction, and the ESWT could reduce chronic pain by changing and reorganizing pathologic memory reactions.¹⁰ Third, ESWT could also have anti-apoptotic effects by affecting upregulation factors and downregulating factors.¹¹ Based on these findings regarding the therapeutic mechanism of ESWT, we assumed that ESWT might cause neovascularization, anti-inflammatory action, tissue regeneration and anti-apoptotic effects in NHO.^7–11

In conclusion, this is the first case report, to our knowledge, which has described the effect of ESWT on NHO in a person with SCI. Thus, these treatments can be a complementary method to conventional therapies including medication, radiation, physical modalities, surgical excision and so on. As this report is on a single case, further studies are recommended that involve larger numbers of subjects with definite standard guidelines regarding ESWT for NHO.

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Contributors None.

Funding None.

Conflicts of interest Authors have no conflict of interests to declare.