A Systematic Review On Comparing Spinal Decompression Surgery And Stem Cell Therapy For Treating Spinal Cord Injuries

Research problem: Spinal cord injuries

Comparing use of stem cell and spinal compression surgery for treating spinal cord injuries

Today I am going to present a discussion on spinal cord injuries and the two most common treatment methods that used for the condition. The presentation will contain information on spinal cord decompression surgery and stem cell therapy and will also discuss about the potential benefits of each. I intend to conduct a systematic review to compare the effectiveness of both the treatment strategies for spinal cord injuries.

I will discuss about the research problem, spinal cord injuries in this slide.

Spinal cord injuries-

• These refer to damages to the spinal cord that bring about temporary or permanent changes in its function.
• Such injuries are found to result in loss of sensation, loss of muscular or autonomic function of body parts (McDonald, Becker and Huettner 2013).
• The injuries can be either complete or incomplete depending on loss of sensation (van den Brand et al. 2012).

Speaker notes- Injury to the cervical vertebra results in paralysis of the four limbs, called ‘Quadriplegia’. Thoracic vertebrae injuries affect the legs and chest and are commonly termed as ‘Paraplegia’. Injury to the sacral region affects the bladder bowel movement, legs, sexual functioning and hips. Complete injuries occur due to loss of function of all cells of the injured areas. Incomplete injuries involve preservation of sensory and motor functions below the injury level. In addition to the aforementioned causes, motor vehicle accidents account for the maximum SCI cases, followed by falls, and sports injuries, such as, shallow water dives. Other potential causes include military conflicts, and iatrogenic injury (improper medical procedure).

There are two primary goals of SCI treatment:

• Relieve pressure on the spinal cord by removing vertebrae portions that are broken or are compressing the cord.
• Stabilizing the spine until the bones get healed (Fujimoto et al. 2012).

This slide will discuss the different causes of spinal cord injuries:

• Physical trauma
• Hyperflexion force
• Hyperextension force
• Lateral stress
• Rotation
• Compression (Chen et al. 2013)
• Distraction

Most SCIs result in compression, contusion or stretch injuries.

Speaker notes- Major manifestations of SCIs include:

• Loss of control over bowel and bladder
• Paralysis
• Inability to move legs and arms (Devivo, 2012)
• Unconsciousness
• Stiffness and pain in neck
• Headache
• Unnatural head positioning
• Signs of shock

Common signs and symptoms also include a burning or tingling sensation in the area below the spinal lesion. Loss of sensation, pain, numbness are also commonly reported (Simpson et al. 2012).

I will discuss about the two major treatments of spinal cord injuries in the follwong slides.

Treatment of SCI- Decompression surgeries:

• Stenosis of narrowing of spinal canal creates numbness, chronic pain and muscle weakness
• Decompression surgery involves removal of the nerves and spinal cord for creating more space for free movement (Minamide et al. 2013).
• Decompression requires 1-3 days of hospitalisation
• Recovery time ranges from 4-6 weeks

Speaker notes- The term encompasses several procedures that are performed with the intent of relieving the symptoms caused due to compression, pressure on the spinal cord and associated nerves. Such surgeries are helpful in relieving the pressure on the spinal cord and nerve roots in 80% cases, thereby reducing the pain symptoms (Fehlings et al. 2012). Major advantages of this surgical method includes minimal morbidity or post-operative discomfort and high rates of success as observed from research evidences (Jones, Wafai and Easterbrook 2014).

We know that there are different types of decompression surgery performed for SCIs, which include laminectomy, foraminotomy, laminotomy, and laminaplasty. While, laminectomy involves removal of bony lamina and thickened ligaments that overlie the spinal cord and nerves, foraminotomy removes bone around neural foramen, particularly used during disc degeneration. The process of laminotomy involves removal of small portion of ligaments and lamina on one side (Polikandriotis, Hudak and Perry 2013) In laminaplasty, the spinal canal is expanded by cutting lamina on one side.

Causes of spinal cord injuries

I will talk about the several drawbacks of spinal decompression surgery that makes it necessary to look for other treatment options for SCI.

Drawbacks of spinal decompression surgery

• Deep vein thrombosis
• Hardware fracture
• Failure of the vertebrae to fuse (Mobbs et al. 2014)
• Bone graft migration
• Persistent pain
• Nerve damage
• Transitional syndrome

I will discuss about the other major form of treatment.

Stem cell therapy

• Based on the objective of replacing lost spinal cells and allowing reconnection in the broken neural circuit
• It helps in regrowing axons (Lu et al. 2012)
• Neural stem cells, embryonic stem cells, mesenchymal stem cells, schwann cells, and induced pluripotent stem cells are used for the purpose (Nakamura and Okano 2013).

Speaker notes- We know that stem cells are defined by their ability to perform self-renewal. They are totipotent in nature. Self-renewal characteristic occurs due to their ability to undergo asymmetric divisions without aging.

This totipotency confers the stem cells with the ability to get differentiated into any cell type (Fujimoto et al. 2012). Endogenous regenerative events that occur after an SCI indicate the fact that the spinal cord takes attempts to repair itself. A surge in local adult stem cell proliferation provides further evidence for the same. Considering the ability of the stem cells to transform into any cell type, they are commonly used for cell replacement therapies in SCIs. Use of embryonic stem cells is preferred over adult stem cells, because the latter will differentiate only into specific kinds of cells. On the other hand, embryonic stem cells can be easily grown in culture.

Stem cells have been found to naturally regenerate the neurons that are lost, thereby generating new supporting cell, which will help in regeneration of the myelin sheath (Nakajima et al. 2012). The cells also acts as a bridge across the injured site and stimulate re-growth of damaged and degenerated axons. Thus, the therapy I discussed above involves delivery of adequate number of stem cells that will travel to the damaged site. This delivery occurs by two routes, namely, Intravenous injection that involves infusion of stem cells into the body by infusing them through the vein (Austin et al. 2012), and Intra-thecal injection with infusion of stem cells through the cerebrospinal fluid by the process of lumbar puncture.

I will discuss about the disadvantages of this stem cell therapy in the slide.

Disadvantages of stem cell therapy-

• Use of stem cells involves destruction of blastocytes formed from invitro fertilisation.
• Adult stem cells would originate only a particular type of cell
• Embryonic stem cells will not be from similar human body and can get rejected

I will discuss about the aims of the systematic review that I intend to conduct and will also talk about the epidemiology of spinal cord injuries.

Aim of the systematic review-

To compare the effectiveness of spinal decompression surgery and stem cell therapy for treating spinal cord injuries

• The worldwide numbers of spinal cord injury ranges from 10.4-83 individuals per million, per year.
• More than 39 people per million in North America are found to suffer from SCI each year (Lee et al. 2014).
• US prevalence rates are approximately 40 cases per million every year (Ma, Chan and Carruthers 2014).

Speaker notes- I aim to conduct a systematic review that will summarise the results from healthcare based research studies together. This will provide a high evidence level and will also help me determine the effectiveness of both the interventions, namely, decompression surgery and stem cell therapy for treatment of spinal cord injuries. Conduction of this systematic review will help me to make judgments about the evidences, followed by making informed recommendations regarding the healthcare scenario. The review will depend largely on the methodology of the included articles and will also measure the health outcomes of the participants. The systematic review will also assist me in judging relevancy and validity of the results, with respect to the research question.

Treatments available: Spinal decompression surgery and stem cell therapy

This is the search strategy that I had adopted while extracting articles.

Search strategy-

Database engine	Search terms	Articles found
Pubmed	‘spinal decompression surgery’ AND ‘spinal cord injury’	148
Pubmed	‘stem cell therapy’ AND ‘spinal cord injury’	26

Speaker notes- The research question was kept as specific and comprehensive as possible to retrieve maximum information from the PubMed database. Specific keywords were determined for searching relevant articles.

Two questions were searched seperately:

‘spinal decompression surgery’ AND ‘spinal cord injury’

‘stem cell therapy’ AND ‘spinal cord injury’

The boolean operator AND was used to find articles that contained information on both the type of intervention and the health conditon. It helped in eliminating irrelevant articles.

These are the inclusion and exclusion criteria that helped me select appropriate articles.

Inclusion and exclusion criteria-

Inclusion criteria	Excluson criteria
• Trials on human or animal models • Spinal cord injuries should be the main focus of the article • Human studies must be done on adults • Must be published in English • Accepted manuscripts will be considered • Must be published not prior to 2011	• Review based articles • Studies conducted on patients aged less than 18 years • Articles published in foreign language • Articles published before 2011 • Abstracts

Speaker notes- Inclusion criteria refer to characteristics or features that should be present in prospective articles that are supposed to be included in the systematic review. On the other hand, exclusion criteria refer to articles that disqualify from the review. The aforementioned inclusion and exclusion criteria were set up to retrieve maximum relevant articles for the same. A time limit of 7 years was taken in order to refine the search and limit the number of relevant articles.

Slide 11-12

I will be present the main findings of the 6 articles that I had selected for the study.

Results from 6 articles-

Articles	Results
Fujimoto et al. 2012	Transplanted hiPS?lt?NES cell?derived neurons restored motor function in mouse model of spinal cord injury. Stem cells helped in reconstruction of the corticospinal tract
Quertainmont et al. 2012	Mesenchymal stem cell grafting showed NGF expression increase, and vascularisation of injured spinal cord tissue
Fehlings et al. 2012	Immediate decompression surgery after SCI showed improved neurologic outcomes (2 grade AIS improvement) during follow-up.
Wilson et al. 2012	2 grade AIS improvement was observed in the SCI patient group subjected to early decompression surgery
Hur et al. 2016	Intrathecal injection of adipose-derived mesenchymal cells improved ASI motor scores in 5 patients and ASI sensory scores in 10 patients
Furlan et al. 2016	Early spinal compression surgery was found to be more cost-effective upon comparison with late spinal compression surgery among SCI patients.

Speaker notes- The article by Fujimoto et al. 2012 stated that using neuronal transplanted cells and neuronal tracers it was found that transplanted hiPS-lt-NES cells are able to differentiate into neural lineages in SCI mouse models and also promote hind limb motor functional recovery.

The objective of the the article by Quertainmont et al. 2012 was to graft MSCs after SCI in adult rats for assessing their effects on functional recovery. Results showed that in MSCs induced open field and grid navigation improvement in the sample group, compared to the controls.

The study by Fehlings et al. 2012 aimed to investigate relative effectiveness of early and late decompression surgery in SCI patients and found that early surgery shows better a ≥ 2 grade improvement (19.8%) compared to late surgery (8.8%).

The article by Wilson et al. 2012 evaluated effects of early versus late decompression surgery on recovery of motor regeneration following SCI. Results showed that greater proportion of patients in early surgery group showed 2-grade ASI improvement.

The article by Hur et al. 2016 evaluated he safety and efficacy of intrathecal autologous ADMSCs in SCI patients and demonstrated improvements in neurological function and absence of any adverse effects.

Advantages and drawbacks of spinal decompression surgery

In the article written by Furlan et al. 2016 a cost-utility analysis was performed for patients subjected to early and late decompression surgery. Results indicated that early decompression is more effective in managing complete and incomplete SCI.

Here are some of the findings of the articles.

Summary findings- Diagrams and Tables

Speaker notes- The above diagrams show the effects of both the procedures on regaining motor control and associated motor improvement in case of spinal cord injuries. The first graph shows that stem cell transplantation helped in limb recovery in SCI mice model in the study conducted by Fujimoto et al. 2012. The graph on the right side shows that SCI mice models showed better locomotion after stem cell grafting in the article presented by Quertainmont et al. 2012. According to the third graph better ASI grade improvements were observed in early decompression surgery performed by Fehlings et al. 2012. The fourth table shows that Wilson et al. 2012 were able to improve ASI grades among SCI patients who were subjected to early decompression surgery.

Early decompression surgery has been found more beneficial in ASI grade improvement, when compared to late decompression surgery. However, regardless of time limits, stem cells have proved efficient in improving motor function.

I present my conclusions from the findings.

Conclusion of the review:

• Spinal decompression may fail for patients with previous history of spinal fusion with instrumentation.
• Decompression also has potential disadvantages related to bone graft migration, persistent pain and nerve damage.
• Stem cell transplantation has several advantages such as abundant supply of mesenchymal stem cells by umbilical cord tissues and lack of chemotherapy drug administration for granulocyte production.
• Thus, stem cell therapy is the recommended procedure for treating spinal cord injuries.

Speaker notes- A thorough analysis of the research articles state that decompression surgery if performed immediately will help in regaining lost spinal cord functions. This is a major drawback. However, there is no time limit for stem cell transplantation. Thus, stem cell therapy is more effective than decompression surgeries in treating spinal cord injuries.

References

Austin, J.W., Kang, C.E., Baumann, M.D., DiDiodato, L., Satkunendrarajah, K., Wilson, J.R., Stanisz, G.J., Shoichet, M.S. and Fehlings, M.G., 2012. The effects of intrathecal injection of a hyaluronan-based hydrogel on inflammation, scarring and neurobehavioural outcomes in a rat model of severe spinal cord injury associated with arachnoiditis. Biomaterials, 33(18), pp.4555-4564.

Chen, Y., Tang, Y., Vogel, L. and DeVivo, M., 2013. Causes of spinal cord injury. Topics in spinal cord injury rehabilitation, 19(1), pp.1-8.

Devivo, M.J., 2012. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal cord, 50(5), p.365.

Fehlings, M.G., Vaccaro, A., Wilson, J.R., Singh, A., Cadotte, D.W., Harrop, J.S., Aarabi, B., Shaffrey, C., Dvorak, M., Fisher, C. and Arnold, P., 2012. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PloS one, 7(2), p.e32037.

Process of stem cell therapy

Fujimoto, Y., Abematsu, M., Falk, A., Tsujimura, K., Sanosaka, T., Juliandi, B., Semi, K., Namihira, M., Komiya, S., Smith, A. and Nakashima, K., 2012. Treatment of a mouse model of spinal cord injury by transplantation of human induced pluripotent stem cell?derived long?term self?renewing neuroepithelial?like stem cells. Stem Cells, 30(6), pp.1163-1173.

Furlan, J.C., Craven, B.C., Massicotte, E.M. and Fehlings, M.G., 2016. Early versus delayed surgical decompression of spinal cord after traumatic cervical spinal cord injury: a cost-utility analysis. World neurosurgery, 88, pp.166-174.

Hur, J.W., Cho, T.H., Park, D.H., Lee, J.B., Park, J.Y. and Chung, Y.G., 2016. Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial. The journal of spinal cord medicine, 39(6), pp.655-664.

Jones, A.D.R., Wafai, A.M. and Easterbrook, A.L., 2014. Improvement in low back pain following spinal decompression: observational study of 119 patients. European Spine Journal, 23(1), pp.135-141.

Lee, B.B., Cripps, R.A., Fitzharris, M. and Wing, P.C., 2014. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal cord, 52(2), p.110.

Lu, P., Wang, Y., Graham, L., McHale, K., Gao, M., Wu, D., Brock, J., Blesch, A., Rosenzweig, E.S., Havton, L.A. and Zheng, B., 2012. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell, 150(6), pp.1264-1273.

Ma, V.Y., Chan, L. and Carruthers, K.J., 2014. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Archives of physical medicine and rehabilitation, 95(5), pp.986-995.

McDonald, J.W., Becker, D. and Huettner, J., 2013. Spinal cord injury. In Handbook of Stem Cells (Second Edition), pp. 723-738.

Minamide, A., Yoshida, M., Yamada, H., Nakagawa, Y., Kawai, M., Maio, K., Hashizume, H., Iwasaki, H. and Tsutsui, S., 2013. Endoscope-assisted spinal decompression surgery for lumbar spinal stenosis. Journal of Neurosurgery: Spine, 19(6), pp.664-671.

Mobbs, R.J., Li, J., Sivabalan, P., Raley, D. and Rao, P.J., 2014. Outcomes after decompressive laminectomy for lumbar spinal stenosis: comparison between minimally invasive unilateral laminectomy for bilateral decompression and open laminectomy. Journal of Neurosurgery: Spine, 21(2), pp.179-186.

Nakajima, H., Uchida, K., Guerrero, A.R., Watanabe, S., Sugita, D., Takeura, N., Yoshida, A., Long, G., Wright, K.T., Johnson, W.E. and Baba, H., 2012. Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury. Journal of neurotrauma, 29(8), pp.1614-1625.

Nakamura, M. and Okano, H., 2013. Cell transplantation therapies for spinal cord injury focusing on induced pluripotent stem cells. Cell research, 23(1), p.70.

Polikandriotis, J.A., Hudak, E.M. and Perry, M.W., 2013. Minimally invasive surgery through endoscopic laminotomy and foraminotomy for the treatment of lumbar spinal stenosis. journal of orthopaedics, 10(1), pp.13-16.

Quertainmont, R., Cantinieaux, D., Botman, O., Sid, S., Schoenen, J. and Franzen, R., 2012. Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions. PloS one, 7(6), p.e39500.

Quertainmont, R., Cantinieaux, D., Botman, O., Sid, S., Schoenen, J. and Franzen, R., 2012. Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions. PloS one, 7(6), p.e39500.

Simpson, L.A., Eng, J.J., Hsieh, J.T. and Wolfe and the Spinal Cord Injury Rehabilitation Evidence (SCIRE) Research Team, D.L., 2012. The health and life priorities of individuals with spinal cord injury: a systematic review. Journal of neurotrauma, 29(8), pp.1548-1555.

van den Brand, R., Heutschi, J., Barraud, Q., DiGiovanna, J., Bartholdi, K., Huerlimann, M., Friedli, L., Vollenweider, I., Moraud, E.M., Duis, S. and Dominici, N., 2012. Restoring voluntary control of locomotion after paralyzing spinal cord injury. science, 336(6085), pp.1182-1185.

Wilson, J.R., Singh, A., Craven, C., Verrier, M.C., Drew, B., Ahn, H., Ford, M. and Fehlings, M.G., 2012. Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study. Spinal cord, 50(11), p.840.