Di Xia, Cheng-Yu Lin, Jin-Yu Gu, Tian-Hao Wan, Kai-Ming Li, Qing Zhang?

1.Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China

2.Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China

Keywords:Lumbar spinal stenosis Neurogenic claudication Non-surgical intervention Interpretation of guidelines

ABSTRACT Lumbar Spinal Stenosis (LSS) is the major cause of Neurogenic Claudication (NC). It is common in the elderly and has an increasing incidence.In 2021, the United States Association for the Study of Pain published new evidence-based clinical practice guidelines to provide more effective nonsurgical treatment of LSS-induced NC.Based on a thorough reading of the latest guidelines, combined with new clinical developments, and in collaboration with the 2011 North American Spine Society,NASS guidelines (hereinafter referred to as the 2011 Guidelines) were compared with the 2019 Danish Health Authority (DHA) Guidelines(hereinafter referred to as the 2019 Guidelines), and the clinical diagnosis and treatment of NC caused by LSS were reviewed and suggestions were put forward.

Lumbar stenosis (LSS) can be divided into primary and secondary causes. Secondary LSS is usually a degenerative process, which can lead to the narrowing of the central spinal canal, lateral recess or intervertebral foramen (or a combination of both), and gradually compress the neurovascular structures in the spinal canal or intervertebral foramen. The characteristic symptom of the disease is neurogenic intermittent claudication (NIC). The patient's walking ability is highly limited and the quality of life is seriously reduced.At present, there are still many disputes about the diagnosis and treatment of NC caused by LSS, among which the efficacy of nonsurgical treatment is quite controversial. In 2021, the American Pain Research Association formulated the non-surgical intervention guide for neurological claudication caused by lumbar spinal stenosis(hereinafter referred to as 2021 Guide), which aims to provide an effective reference for the non-surgical treatment of LSS. The guide uses grade evidence quality classification to understand the level of evidence and the strength of recommendations.

1. Introduction

Lumbar spinal stenosis is mainly characterized by slow-onset and persistent low back pain and leg pain, intermittent claudication, and limited lumbar movement. Low back pain can occur in the lower waist and sacrum. Leg pain is mostly bilateral, alternating on both sides, or light on one side. The nature of pain is mostly soreness,tingling or burning pain, among which intermittent claudication is the characteristic symptom of the disease. Patients may have positive back extension test and positive straight leg elevation test. It can also be accompanied by lower limb muscle atrophy, weakening or disappearance of pain on the outside of the lower leg, and weakening or disappearance of Achilles tendon reflex. However,some patients may not have any positive signs. CT and MRI are helpful to clarify the diagnosis and provide quantitative criteria.

Research shows that for some patients with NC caused by LSS,the effect of surgical treatment is faster than that of non-surgical treatment in the first three months, which can effectively reduce the pain of lower waist and lower limbs in a short time, improve the symptoms such as intermittent claudication and improve the quality of life of patients, but the clinical benefit may not exceed 4-8 years, and the reoperation rate can reach 12.83% [1,2].During decompression surgery, the incidence of cardiorespiratory complications and stroke in the elderly is about 2%. The common complications are infection, tissue adhesion, cerebrospinal fluid leakage and so on; The mortality rate can reach 0.5% [3,4]. The spine Committee of the World Federation of Neurosurgical Societies(WFNS) suggests that there are no surgical indications (① persistent or intermittent pain that cannot be relieved by conservative therapy;② progressive neurological changes; ③ cauda equina syndrome;④ complicated with lumbar disc herniation, with severe symptoms,affecting life and workers.) Patients with LSS, as well as patients who cannot tolerate or refuse surgery, should first choose the conservative treatment based on medical exercise. When the clinical symptoms do not improve after conservative treatment for more than 3 months, surgical treatment can be considered. For patients with mild symptoms, the effect of drug treatment and interventional therapy is better than surgical treatment.

The 2021 guidelines provided by the American Pain Research Association developed 6 recommendations based on the results of randomized controlled trials and 5 recommendations based on professional consensus, which are summarized into 3 general recommendations: (all recommendations are conditional and weak recommendations)

Recommendation 1: for patients with NC caused by LSS, clinicians and patients can initially choose non drug treatment for multimodal rehabilitation, including doctors' education and suggestions for patients, changes in patients' lifestyle and behavior, family exercise,manual treatment and rehabilitation (medium quality evidence), or traditional acupuncture and moxibustion treatment (very low quality evidence), Postoperative rehabilitation and cognitive behavioral therapy (CBT) 12 weeks after operation (very low quality evidence).Recommendation 2: for patients with NC caused by LSS, clinicians and patients can try to use serotonin norepinephrine reuptake inhibitors (such as duloxetine) or tricyclic antidepressants (such as amitriptyline, noramitriptyline, etc.) (very low quality evidence).

Recommendation 3: for patients with NC caused by LSS, the guidelines do not recommend the use of the following drugs:nonsteroidal anti-inflammatory drugs, Mecobalamin, calcitonin,paracetamol, opioids, muscle relaxants, pregabalin (based on consensus), gabapentin (very low-quality evidence) and epidural steroid injection (high-quality evidence).

2. The 2021 guideline first proposed multimodal rehabilitation intervention

The 2021 guidelines suggest that for LSS and NC patients with or without low back pain, a combination of education and advice,manual therapy and home exercise can be provided to improve walking ability and physical function (medium quality evidence).Multimodal therapy is a new concept introduced in the 2021 guidelines, which has not been discussed in the previous two editions of the guidelines.

Three RCTs were included in the 2021 guideline. Ammendolia et al. [5] randomly divided the patients into comprehensive group and autonomous group. The trial showed that the comprehensive group showed greater improvement on the ODI walking scale at six months; Schneider [6] and others randomly divided the patients into three groups, which were given routine medical care, individualized manual treatment and rehabilitation exercise, and communitybased group practice. Although these three measures can improve walking ability in the long term, compared with the other two groups, individualized manual therapy and rehabilitation exercise can improve symptoms, physical function and walking ability in the short term. Minetama et al. [7] also compared the effectiveness of supervised physical therapy (PT) and unsupervised exercise in patients with LSS. Compared with unsupervised exercise, patients receiving Pt had significant improvements in symptom severity,physical function, walking distance, pain and physical activity.

The new guidelines believe that multimodal rehabilitation intervention can reduce pain, improve function and improve quality of life. The guidelines suggest that after considering the potential risks and patients' intentions, phased treatment should be provided,and multimodal rehabilitation should be taken as the first-line treatment, combined with single or combined medication. After the treatment plan, you should maintain daily home exercise and selfcare.

3. Acupuncture therapy is recommended by the new guidelines

The new guidelines suggest that for LSS and NC patients with or without LBP, traditional acupuncture can be considered to improve pain and physical function in the short term (very low quality evidence). Considering that the evidence quality of these two small RCTs is very low and there is insufficient evidence to recommend or oppose acupuncture treatment, the 2011 guideline [8] does not recommend acupuncture therapy. However, these two studies can show that acupuncture can significantly improve the pain and dysfunction symptoms of degenerative LSS in the short term.

Compared with the 2011 guidelines, the new guidelines include two latest RCTs. In a 2020 RCT [9], the acupuncture group significantly improved the disability at 8 weeks and 3 months, but the curative effect did not further improve at 6 months. In addition,after acupuncture treatment, the patient's back, hip and leg pain were improved. In another RCT [10] in 2018, the patients were divided into drug group (acetaminophen), exercise group and acupuncture group.The symptoms of the three groups were significantly improved,but only the improvement of physical function was found in the acupuncture group.

4. The new version of the guide emphasizes the importance of functional exercise

According to the new guidelines, postoperative functional rehabilitation with cognitive behavioral therapy (CBT) at 1 and 12 months after operation can reduce pain and improve function (lowquality evidence). At the same time, for patients with LSS with LBP, on the one hand, exercise can alleviate short-term pain and dysfunction, on the other hand, appropriate exercise can reduce patients' stress, fear and anxiety and improve patients' self-identity[11]. The 2011 guidelines recommend providing patients with active limited courses of physical therapy (education and exercise). The 2019 guidelines [12] believe that exercise is generally beneficial to health and has no adverse effects. It is recommended to provide supervised rehabilitation treatment for patients with lumbar spinal stenosis before and after operation. The new guidelines include an RCT by monticone et al. [13], which shows that compared with simple exercise, exercise combined with CBT has more advantages in alleviating pain, improving dysfunction and thinking disorder, and improving quality of life.

5. Medicaton

At present, the non-surgical intervention of NC caused by LSS is still based on drug treatment, and the new guidelines also make new recommendations on the use of drugs. 2021 guidelines do not recommend the use of non steroidal anti-inflammatory drugs,Mecobalamin, calcitonin, paracetamol, opioids, muscle relaxants,pregabalin, gabapentin and other drugs to treat NC caused by LSS.It is recommended to try to use serotonin norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAS). See Table 1 for specific recommendations:

Table 1 Drug treatment recommendations for NC caused by LSS in the new guidelines

6. Epidural steroid injection

Lumbar epidural steroid injection can be carried out through three ways: lamina, caudal or interlaminar. Under the guidance of fluoroscopy, glucocorticoids (such as triamcinolone acetonide 60-120 mg, betamethasone 6-12 mg, dexamethasone 8-10 mg or methylprednisone 60-120 mg) are usually injected, and 1-3 ml of 0.25% - 1% lidocaine can be used for anesthesia or no anesthesia can be used during injection.

The 2021 guideline considers that the evidence of esis is moderately deterministic, but the ideal effect is not clear (some evaluations do not meet MCID), the adverse effect is small, and there are few reports of adverse events. At the same time, the resources, costs and training requirements for epidural steroid injection must be considered, and it is not easy to carry out epidural steroid injection in remote areas or smaller medical centers. Recent studies have shown that epidural steroid injection did not show significant inter group differences. If the pain did not improve in the first 6 weeks,continuing any type of epidural injection will not improve long-term symptoms. In addition, esis can also lead to decreased bone mineral density and increased fracture risk [17]. ESI should be carefully considered for patients at risk of osteoporotic fracture (such as postmenopausal women). Therefore, the 2021 guideline does not recommend the use of epidural steroid injection for short-term pain relief and function improvement.

The 2011 guidelines suggest that for patients with neurogenic claudication or radiculopathy, intralaminar epidural steroid injection can provide short-term (2 weeks-6 months) symptom relief, but the evidence for long-term (21.5-24 months) efficacy is contradictory(recommendation level B). For patients with radiculopathy or neurogenic intermittent claudication caused by lumbar spinal stenosis, multiple injection schemes of epidural steroid injection or caudal vein injection through intervertebral foramen under X-ray guidance are recommended to obtain medium-term (3-36 months)pain relief (recommendation level: C).

7. Future research directions and Prospects

1) Future studies should aim to identify and verify the clinical manifestations of LSS, stage the clinical manifestations in combination with imaging, and the correlation between the severity of symptoms and anatomical lesions. It is more suitable for the patients to be treated conservatively through imaging. The symptoms of patients have strong subjectivity. Relatively speaking, the degree of anatomical structure change is a more objective index, which can provide a unified quantitative standard for clinical diagnosis,treatment and research.

2) The therapeutic effect of acupuncture and moxibustion on LSS needs further research. The 2011 guidelines found insufficient evidence to support acupuncture treatment, while the 2019 guidelines did not assess this treatment. A meta-analysis published in 2019 showed that acupuncture treatment may be beneficial to LSS,but the included studies were mainly a single small RCT, and the safety evaluation of acupuncture treatment could not be made [18].Although the 2021 guidelines suggest that acupuncture treatment can be provided to willing patients, the existing RCT can only provide very low-quality evidence, and the main performance is short-term improvement, which can not prove its long-term therapeutic effect.At the same time, the existing RCTs are mainly limited to Asia, and whether the test results can be extended to a larger LSS population remains to be further studied.Based on a number of RCTs and professional consensus, the 2021 guidelines provide 11 specific recommendations and the latest evidence for the non-surgical treatment of neurogenic claudication caused by lumbar spinal stenosis. Compared with the previous two versions of the guidelines, the guidelines advocate multimodal rehabilitation intervention; It is suggested to use acupuncture therapy and provide guidance for the acupuncture position; When carrying out drug treatment, we should choose carefully. In clinical practice,we should take the guidelines as a reference, combined with the specific situation of patients, and choose the most reasonable treatment according to individual conditions. When patients have serious symptoms or non-surgical treatment is ineffective, surgical decompression should be carried out in time.

Author's contribution

Xia Di, Lin Chengyu, article conception and design, feasibility analysis; Gu Jinyu, Wan Tianhao and Li Kaiming search and translate the guide; Xia Di is responsible for the analysis of the guide, writing and revising the paper; Zhang Qing and Lin Chengyu are responsible for the quality control and proofreading of articles.There is no conflict of interest in this article.