Uppsala Spinal Stenosis Study
Phase: NA
Conditions: Spinal Stenosis, Spinal Stenosis Lumbar, Degeneration Lumbar Spine, Degeneration Spine, Neurogenic Claudication Co-Occurrent and Due to Spinal Stenosis of Lumbar Region, Pseudoclaudication Syndrome
Sponsor: Uppsala University

 
 
Uppsala Spinal Stenosis Study (UppSten) 
 
 
Decompression vs Non-surgical treatment for 
the lumbar spinal stenosis. An RCT with 
clinical, radiological, neurophysiological, 
histologic and biochemical follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
         Uppsala, 2018-03-28 

Background 
 
Lumbar spinal stenosis (LSS) is characterized by low back and leg pain, walking disturbances 
and sometimes instability, impaired balance and numbness of the lower limbs. This condition 
is caused by degenerative changes in the lumbar spine including bulging discs, osteophytes 
from the arthritic facet joints and thickened ligamentum flavum which together cause 
narrowing of the spinal canal and thus affect the lumbar nerve roots. LSS affects mainly older 
populations and is unusual under 50 years old. This diagnosis is attracting more and more 
interest due to the aging population with increasing demands for physical activity. LSS is the 
most common indication for spinal surgery. The surgical treatment involves relieving the 
pressure from the nerve structures in the stenotic segments through a posterior approach. The 
hypertrophic ligaments and parts of the facet joints are removed (i.e., decompression). Adding 
fusion to the decompression for stabilization of the decompressed segment has not been 
shown to provide superior results than decompression alone [Försth] [Sigmundsson]. In 
several studies, surgery has been shown to have better results than the conservative treatment 
[Weinstein] [Malmivaara]. However, methodological difficulties and a large proportion of 
cross-over in these studies indicate that there is still uncertainty about whether surgery is 
generally a better option. 
 
After decompression, only 60-70% of patients reported to be satisfied with the result and a 
minor proportion of them experienced even no improvement at all [Strömqvist]. Conservative 
treatment has shown in some studies to have good results for some patient groups [Delitto] 
and other studies have shown that the benefit of the surgical treatment decreases over time 
[Slätis] and that physical exercise may reduce the need for surgery [Nord]. Moreover, surgery 
itself has a positive placebo effect that can improve symptoms in some diseases [Harris]. 
 
It has been speculated whether the compression of the nerve roots causes in some patients 
permanent nerve damage with muscle denervation, while in other cases a reinnervation and 
recovery of the function may occur. Results from neurography and EMG studies have been 
shown these modalities to have a possible predictive value for the natural process of LSS 
[Adamova]. If a neurophysiological examination could be able to predict which patients are 
able to benefit from surgery, many patients could avoid surgery and the risks involved in it. 
 
The degeneration of the lumbar spine is progressively impairing the spinal sagittal balance. 
The need to make extensive correction and fusion in addition to the decompression in order to 
restore the sagittal balance is debated among spinal surgeons. The experience gained from 
previous RCTs is that the patients’ back pain is reduced by decompression only [Försth]. 
Many patients also report that their posture improved after decompression alone. 
 
Previous trials in the connective tissue and blood samples have shown that proinflammatory 
factors and nociceptors (molecules that induce pain) are upregulated in patients with patellar 
tendinosis which is an inflammatory condition [Lian] [Schizas] [Schizas]. Changes in the 
connective tissue that cause LSS are mainly inflammatory (arthritic facet joints and 
ligamentum flavum) and a possible theory around LSS pathophysiology may be that the 
nerves are biologically affected by proinflammatory factors and nociceptors. Identification of 
some of these factors could lead to better explanation of the pathomechanism behind the 
nerve compression in LSS and to the development of future pharmacological treatments to be 
used in conjunction with surgery. 
 
 

Aims 
 
The aim of this study is primarily to evaluate whether surgery with decompression leads to 
superior results than the non-surgical treatment with structured physical therapy. For this 
evaluation, the Oswestry Disability Index (ODI) will be used. 
 
The main secondary aim is to investigate by means of Neurography and EMG, whether the 
degree of neurological affection caused by nerve compression affects the outcome of surgery 
for LSS. 
 
The questions at issue are: 
 
1. Does decompression provide a better clinical outcome than the non-surgical treatment? 
2. Is there any correlation between the grade of the clinical symptoms and the degree of 
neurological affection measured by ENG/EMG? 
3. Is there any connection between the neurological affection and the proinflammatory 
markers/nociceptors in the blood as well as in histological findings from ligamentum flavum? 
Are these correlated with the grade of the clinical symptoms? 
4. Does decompression provide superior neurological recovery, measured by ENG/EMG, in 
comparison to the non-surgical treatment? 
5. Can decompression improve the spinal sagittal balance? 
 
Inclusion criteria 
 
1. Age 50-85 years. 
2. Clinical symptoms of lumbar spinal stenosis (pseudoclaudication) that indicate and 
motivate surgery. NRS in lower limbs ≥3. 
3. MRI with finding of LSS at 1-3 lumbar levels. Dural sac area ≤ 75 mm² or degree of 
stenosis C or D according to Schizas classification. 
4. The surgical treatment to be provided is decompression alone. 
5. The patient has given oral and written informed consent to the participation in the study. 
 
Exclusion criteria 
 
1. Degenerative deformity with Cobb angle > 20°. 
2. Spondylolysis. 
3. Symptomatic osteoarthritis of the lower limbs that affects and limits their function. 
4. Arterial insufficiency (claudication intermittent). 
5. Past lumbar surgery other than disc herniation. 
6. Conditions that affect the spine such as ankylosing spondylitis, Diffuse Idiopathic Skeletal 
Hyperostosis (DISH), spondylodiscitis/infections, malignancy, neurological diseases. 
7. Heart and lung diseases that present a significant risk for surgery or make it impossible for 
the patient to take part in physical training program (ASA>3). 
8. Polyneuropathies.  
9. Psychological factors that make the patient incapable of inclusion in the study (eg drug 
addiction, dementia)  
 
 
 
 

Outcomes 
 
Primary outcome: Oswestry Disability Index (ODI) 
 
Secondary outcome:  
Neurophysiology: Primary outcome measure: 1) Motor amplitude (neurography) and 2 ) 
Degree of Denervation Activity (EMG). Secondary outcomes: Sensory amplitude, F response 
latency and H-reflex (neurography), number of motor units (MUNIX) and degree of 
reinnervation (EMG).  
 
From the Swedish Spine Registry (Swespine): EQ-5D, Back pain (NRS), Leg pain (NRS), 
Subjective walking ability, Global Assessment (GA), Satisfaction 
 
Objective walking ability (6-Minute Walk Test-6MWT)  
Radiological: Lumbar Lordosis (LL) and Sagittal Vertebral Axis (SVA) 
 
Follow-up 
 
6 months, 1, 2 and 5 years 
 
The results at 2 years will be the most important goal of the study, on which the main clinical 
results will be built. The neurophysiological results can be analyzed and presented after the 6-
month follow up. 
 
Power calculation 
 
Totally 150 patients will be included, 75 in each treatment group. The study size has been 
calculated with power 80% and alpha = 0.05 as well as an ability to detect 12 units (SD19) of 
difference in the ODI, giving 40 follow-up patients in each group. Experience from previous 
registry-based RCTs within Swespine, regarding loss to follow-up and cross-over (ie patients 
admitted to non-surgical treatment who wish to switch to surgical intervention), is taken into 
account. According to this, the loss is considered to be low (<5% after 2 years) [Försth]. In 
previous studies, this proportion was comprised of 9 to 40% of the conservatively treated 
patients [Weinstein] [Malmivaara]. Loss to follow-up and cross-over are estimated to be up to 
50%, which leads to 75 patients needed in each group.  
 
Each year, 100-130 patients who meet the inclusion criteria are operated at the Department of 
Orthopaedics  (Uppsala University Hospital and  + Enköping Hospital). We estimate that 150 
patients will be recruited to the study within a period of 24 months.  
 
 
Flow-chart 
 
Recruitment 
The patient is recruited during an outpatient visit to a surgeon. Oral and 
written information about the study is given. 
ICF  
The patient gives oral and written consent. The consent is documented in 
the patient journal and the written consent is filed in the study document 
binder. 
Baseline data 
- PROMs via Swespine Study 
- 6MWT 

- Scoliosis standing digital X-rays (AP and lateral views) 
- ENG/EMG 
- Blood samples for analysis of inflammatory markers (OLINK) 
 
Randomization 
Simple block randomization to the two treatment arms. 
 
Treatment arms 
A. Decompression. Central decompression of the stenotic segments 
with undercutting of the lateral recesses, free mobilization, and 
routine follow-up postoperatively by physiotherapist. 
 
B. Non-surgical treatment. Exercise on exercise bike according to 
the "Östersund model" [Nord] 30 min, 3 times/week for 4 months.  
 
 
Follow-up 6 months 
- PROMs via Swespine Study 
- 6MWT 
- Scoliosis standing digital X-rays (AP and lateral views) 
- ENG/EMG 
- Blood samples for analysis of inflammatory markers (OLINK) 
 
Cross-over 
Feasibility for cross-over from group B till A after 6-month follow-up. 
 
Follow-up 1,2 years 
- PROMs via Swespine Study 
- 6MWT 
 
Follow -up 5 years 
- PROMs via Swespine Study 
 
In the treatment group A, in conjunction with the surgical procedure, ligamentum flavum will 
be collected (which is routinely removed during the decompression surgery) and will be 
examined with histological methods regarding proinflammatory markers and nociceptors. An 
1x1 cm tissue piece will be dissected and saved. The ligament samples will be examined by 
immunohistochemistry and with proteomics analysis. Proteomics analysis will be performed 
in collaboration with Olink Uppsala (www.olink.com) where 92 inflammation-related factors 
will be investigated. Sample management will be in accordance with the Ethics Examination 
Act of Human Research (2003: 460) and according to the rules of Uppsala Biobank. 
 
References 
 
Försth P, Michaëlsson K, Sandén B. 
Does fusion improve the outcome after decompressive surgery for lumbar spinal stenosis?: A 
two-year follow-up study involving 5390 patients. Bone Joint J. 2013 Jul;95-B(7):960-5. doi: 
10.1302/0301-620X.95B7.30776. 
Försth P, Ólafsson G, Carlsson T, Frost A, Borgström F, Fritzell P, Öhagen P, Michaëlsson K, 
Sandén B. 
A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis. N Engl J 
Med. 2016 Apr 14;374(15):1413-23. doi: 10.1056/NEJMoa1513721. 
Sigmundsson FG, Jönsson B, Strömqvist B. 
Outcome of decompression with and without fusion in spinal stenosis with degenerative 

spondylolisthesis in relation to preoperative pain pattern: a register study of 1,624 patients. 
Spine J. 2015 Apr 1;15(4):638-46. doi: 10.1016/j.spinee.2014.11.020. 
Malmivaara A, Slätis P, Heliövaara M, Sainio P, Kinnunen H; Finnish Lumbar Spinal 
Research Group. 
Surgical or nonoperative treatment for lumbar spinal stenosis? A randomized controlled trial. 
Spine (Phila Pa 1976). 2007 Jan 1;32(1):1-8. 
Weinstein JN, Tosteson TD, Lurie JD, Tosteson AN; SPORT Investigators. 
Surgical versus nonsurgical therapy for lumbar spinal stenosis. 
N Engl J Med. 2008 Feb 21;358(8):794-810. doi: 10.1056/NEJMoa0707136. 
Strömqvist B, Fritzell P, Hägg O, Jönsson B, Sandén B; Swedish Society of Spinal Surgeons. 
Swespine: the Swedish spine register : the 2012 report. 
Eur Spine J. 2013 Apr;22(4):953-74. doi: 10.1007/s00586-013-2758-9. 
Delitto A, Piva SR, Moore CG, Fritz JM, Welch WC. 
Surgery versus nonsurgical treatment of lumbar spinal stenosis: a randomized trial. 
Ann Intern Med. 2015 Apr 7;162(7):465-73. doi: 10.7326/M14-1420. 
Slätis P, Malmivaara A, Heliövaara M, Sainio P, Herno A. 
Long-term results of surgery for lumbar spinal stenosis: a randomised controlled trial. 
Eur Spine J. 2011 Jul;20(7):1174-81. doi: 10.1007/s00586-010-1652-y. 
Nord T, Kornerup U, Grönlund P, Reuterwall C. 
Exercise reduced the need for operation in lumbar spinal stenosis. Circulatory load in the 
form of cycling gave good effect. Lakartidningen. 2015 Jan 27;112. pii: C7XP. Swedish.   
Harris, I. 
(2016). Surgery, the ultimate placebo (1st ed., pp. 80-112). 
 
Micankova Adamova B, Vohanka S, Dusek L, Jarkovsky J, Bednarik J.  
 
Prediction of long-term clinical outcome in patients with lumbar spinal stenosis. 
Eur Spine J. 2012 Dec;21(12):2611-9. doi: 10.1007/s00586-012-2424-7 
 
Lian Ø, Dahl J, Ackermann PW, Frihagen F, Engebretsen L, Bahr R.  
Pronociceptive and Antinociceptive Neuromediators in Patellar Tendinopathy. Am J 
Sports Med. SAGE PublicationsSage CA: Los Angeles, CA; 2006 Nov 
30;34(11):1801–8 
 
Schizas N, Lian Ø, Frihagen F, Engebretsen L, Bahr R, Ackermann PW.  
Coexistence of up-regulated NMDA receptor 1 and glutamate on nerves, vessels and 
transformed tenocytes in tendinopathy. Scand J Med Sci Sports. 2009 Apr 14;20(2):208–15. 
 
Schizas N, Weiss R, Lian Ø, Frihagen F, Bahr R, Ackermann PW.  
Glutamate receptors in tendinopathic patients. J Orthop Res. 2012 Sep;30(9):1447–52.