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Should you have physiotherapy after surgery?

by A Badran

At present, surgery is the mainstay of treatment for myelopathy.  Whilst it is able to stop further injury to the spinal cord by relieving impingement, the limited capacity for the spinal cord to repair leads to only partial recovery.  Therefore strategies to improve recovery after surgery are a major unmet need in myelopathy. 

This has generated much interest in postoperative therapies to maximise postoperative recovery, including the development of neural repair medicines.  Unfortunately, whilst showing early promise, these are not yet ready for every-day use. 

Physiotherapy on the hand, is routinely employed for many related health conditions, and is considered to significantly contribute to recovery after conditions such as Stroke and Spinal Cord Injury. 

Our ambition therefore was to look at the medical literature to see if there was any suggestion it could be of benefit to patients with myelopathy. 

How did we go about this?

We performed something called a systematic review and this has recently been published in the journal of Clinical Rehabilitation. (1)  This is a research technique which rigorously screens databases of medical literatures.  Typically this is done in three stages:  Firstly, a search strategy (string of relevant words) is put together.  This is then applied to medical literature databases and the results of the search are manually screened, initially by their title and summaries.  Any articles considered potentially relevant and then read in full to evaluate their relevance to the research question.  

What did we find?

​We found only one study commenting on the effects of physiotherapy after surgery for DCM. This is a small retrospective study of 21 patients with DCM that underwent surgery and then rehabilitation. However it was a poor quality study, and spontaneous recovery after surgery could not be distinguished from the effects of physiotherapy specifically. Although the study concluded that rehabilitation improved functional status, the small study size and its design make this conclusions very tentative.

Therefore, unfortunately, we identified that the effect of postoperative physiotherapy in DCM has been poorly studied and we could not make any recommendations about whether it should be routinely provided. This does not mean that physiotherapy is harmful or should not be provided after surgery for degenerative cervical myelopathy but simply more investigation is required.  

Pleasingly there are now two registered randomised controlled trials, one in Taiwan and another in Canada, which will hopefully shed light on the effects of postoperative rehabilitation in DCM.

References

Hydrotherapy brings green shoots of recovery to exercise desert.

PictureDelphine Houlton

By Delphine Houlton

On completion of my first ACDF, the surgeon immediately informed my anxious husband that I would never ride a bike again.
That was in 2007 and, to be fair, I have not taken to the saddle since.  After initial improvements, unfortunately many Degenerative Cervical Myelopathy (DCM) symptoms returned. Fusion had not taken place and the discs had slipped slightly.
On discharge from my second ACDF in 2008, with discs caged and this time a soft collar for six weeks, I was told not to put any strain on my neck at all. I still had balance/walking problems and numbness alongside other symptoms.
Neither my GP nor my neurologist ever contradicted the “no strain on the neck” message. Although I did learn that if I had MS I would have been immediately offered physiotherapy and hydrotherapy.

So, I dutifully did not put strain on my neck for more than eight years – my symptoms worsened as I gained weight, and felt rubbish, in an exercise desert.

​After all, logically, the gym was out of the question – I would have fallen over if I had gone on the treadmill thanks to the balance problems. Even in the shopping centre my legs seized up after a three-minute slow and painful walk. Furthermore, my favourites in a previous life, rowing machines and swimming certainly put strain on the neck, as did all weight-training equipment. 

Giving up work and becoming more housebound, in total frustration, I found a private physiotherapist and explained the problems. She was knowledgeable and caring. I worked hard to strengthen my core muscles, improve my balance and more. However, progress was slow and, to be honest, the exercises boring in the longer term. However, she had opened a window of possibility.



I asked my GP directly for a referral for hydrotherapy and she agreed. 
Six months later I was standing chest-deep in warm water – stretching, balancing, walking forwards, sideways and backwards, bending my knees, practising going up and down a step in the pool, sitting on a chair and cycling with my legs and relaxing every muscle as I floated. Movements I had struggled with, or avoided on land for years, were all possible.
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Hydrotherapy


The goal, I was told, was to revive muscle memory. Taking advantage of the ease of movement in the warm water, I was reminding all my muscles how they should be working in a whole range of manoeuvres I found impossible out of the water.

My initial six sessions gave me the confidence, and the ability, to tackle so much more out of the water too. 
Additional sessions have built up my strength and confidence even further. 
I can now tackle many tasks in the garden, go for a short walk on uneven ground in the countryside, and walk up and down stairs without too much discomfort or fear of falling. I can even bend enough to put on boots, socks and tights again! 

Of course, there are still not-so-good days when I need to think harder about where all my limbs are and how to move them. However, the confidence I have regained through hydrotherapy keeps me going and keen to take on more physical challenges at every possible opportunity. 

Unsurprisingly, my mood too has greatly improved – I see a much brighter future ahead rather than the gloom and frustration of a continuing decline in physical abilities and increasingly limited lifestyle.
The transformation hydrotherapy has brought to my exercise desert is clearly anecdotal evidence. Proper research is needed into the benefits of hydrotherapy for people with DCM. 
If hydrotherapy can be shown to improve outcomes, and relieve low mood associated with limited lifestyles, then we must push for the option of hydrotherapy to be incorporated into all DCM post-operative treatment programmes. It also possibly has the potential to help relieve pre-operative problems too.


    Have you used hydrotherapy?
    If so we would like to hear about your experience?

Living with long term conditions like myelopathy

 BY Dr Amalia Gasson
​   
Amalia has been working in adult mental health in the NHS for eight years, currently working in a community mental health rehabilitation team.  She is experienced in working therapeutically with clients with a wide range of difficulties, with a focus on anxiety, depression, relationship difficulties and serious mental health difficulties. She also has an interest in chronic pain and physical health conditions and has completed research into chronic fatigue syndrome. 

Life is stressful. Every day there are lots of events that will fill up our “stress buckets” to varying levels…the computer stops working, we drop a cup, there’s a queue in the shop.
If we have had a bad night’s sleep our stress bucket is already part full before we get out of bed.
Living with long term health conditions means we may have buckets almost overflowing to start the day with and then one “small” stress makes that bucket overflow and everything feels impossible to cope with.

Finding ways to manage our stress levels reduces those times of feeling overwhelmed. It can also have a positive impact on our physical health. There are many very good online resources with tips and techniques that you may find helpful.

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Dr Amalia Gasson: Clinical Psychologist

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Managing energy levels
With any health condition, there is a significant impact on our energy levels. Generally, we tend to go through life doing the most we can in the shortest time. Then our health can stop us in our tracks.
Learning to manage our energy so it feels less of a rollercoaster and more predictable can be tricky. This site has a whole range of self help resources. This link is specifically to the cycles we get into which can make managing energy difficult, and ways to make changes:

https://www.getselfhelp.co.uk/chronicfp.htm

Spoon Theory is another approach to managing energy
https://butyoudontlooksick.com/articles/written-by-christine/the-spoon-theory/


Pain

Managing pain levels, like fatigue, links to the ideas of pacing and spoon theory. There are also specific resources about pain such as:
http://www.moodjuice.scot.nhs.uk/ChronicPain.asp

The pain toolkit is created by someone who experiences chronic pain. There are videos on this site and also a pdf download: https://www.paintoolkit.org/tools

The British Pain Society also has helpful information: https://www.britishpainsociety.org/

Mindfulness
It feels like you can’t go anywhere nowadays without hearing someone talking about mindfulness. This is an approach developed from eastern Buddhist meditation techniques and applied to pain management. It was found to be so helpful it has spread throughout healthcare as a way of managing stress.
At its core is a very simple idea, which is surprisingly difficult to put into practice: “Be in the present moment.”

Most of the time we are caught up in thoughts or regrets about the past, or worries about the future, and rarely notice the present. 

​Have you ever driven somewhere, arriving without remembering the journey? Have you ever been reading a book without taking it in? Looking at your watch without actually seeing the time? These are all examples of being “mindless” which is the opposite of being mindful. 

There are some good links about mindfulness here, and several downloads and resources to listen to:
https://www.mindful.org/what-is-mindfulness/
https://www.getselfhelp.co.uk/mindfulness.htm

There are many mindfulness books available. In my work I tend to use Mindfulness for Dummies, by Shamash Alidina, as it is so practical.

One very simple mindfulness practice is to go through all your senses, focusing on each one in turn. By doing this you are totally absorbing yourself in the present, even if only very briefly. 

I’m also a fan of the mindful eating idea, often done with a raisin but this one uses chocolate
https://www.jmu.edu/counselingctr/files/Mindful%20eating.pdf 

A great article from Brain & Life (American academy of neurology) on meditation called Inner peace.
Brain & Life 

We now have our very own INSIGHT TIMER group  for Cervical Myelopathy you can join by entering your details in the form belowCervical Myelopathy you can join by entering your details in the form below


Do you want to join our very own insight timer meditation group? if so please fill in your details below

Compassion
How kind are you to yourself?
When you are having a tough day, do you congratulate yourself on what you manage despite that, or do you have a go at yourself for struggling?

As humans we are generally pretty rubbish at being kind to ourselves. An approach called compassion focused therapy is based on how the human brain evolved and explains why we are so tough on ourselves. 

Paul Gilbert, who developed this approach, believes in sharing all the resources and information:
https://compassionatemind.co.uk/

A summary of compassion focused therapy ideas can be found at :
https://www.getselfhelp.co.uk/compassion.htm
There are some nice worksheets on becoming aware of your levels of criticism and compassion practices under therapist resources at: https://www.actwithcompassion.com/therapist_resources

The centre for clinical interventions is an Australian site with excellent self help workbooks for a whole range of issues including building compassion, managing panic, dealing with distress and overcoming perfectionism (a character trait many of us have but which makes pacing energy nigh on impossible so definitely worth a quick look): http://www.cci.health.wa.gov.au/resources/consumers.cfm
Most have simple questions in the first module to help you assess whether this is a specific area that might be helpful for you to explore further.

Finally, the great thing about the internet is just how many resources there are.
You may have come across many that you could share on a forum like this to help others. 

There are also great Apps like Headspace which talk you through mindfulness exercises.
This is a list of Apps recommended by the NHS: https://www.getselfhelp.co.uk/links2.htm

Here is a list here of mindfulness apps:
 https://www.healthline.com/health/mental-health/top-meditation-iphone-android-apps

If you feel you want further support for your mental health and ways of managing stress, a good first point of contact is your GP who can refer on to primary care therapy. 
There are many parts of the UK where you can also refer yourself – the NHS website has a service finder:

https://www.nhs.uk/Service-Search/Psychological-therapies-(IAPT)/LocationSearch/10008

Mind often offer free courses and support: https://www.mind.org.uk/
The Samaritans have useful information on their site https://www.samaritans.org/, have the phone number 116123 and you can email jo@samaritans.org (they aim to respond to email within 24 hours).

In crisis 
If you feel you are in crisis with your mental health and you are
having – suicidal thoughts and feelings; or thoughts about harming yourself or someone else; or you have seriously hurt yourself…
You can go to any hospital A&E department and ask for help (if you need to, call  999  and ask for an ambulance). There are specialist mental health liaison teams in hospitals who will see you quickly and be able to offer the most appropriate support

Spinal Cord Swelling: What is it?  Does it matter?

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By B.Samara 
Swelling is a common reaction of your body to any form of injury; remember the last time you banged your finger, or perhaps twisted your ankle?  So unsurprisingly, it can happen to the spinal cord and has been reported in patients with CSM.  However, it is not present in all patients and its significance is not certain.  In addition to this, some studies have now described that the spinal cord can swell after surgery.  The reason for this is unclear and equally what it means for patients is not clear. 
 

On basic MRI imaging, swelling is not that easy to detect; a doctor may look for a slight enlargement of the spinal cord or some signal change.  An alternative method is to inject a ‘contrast agent’ into the patient during the scan.  This is a special form of dye which highlights certain processes, and can be a indicator of swelling amongst other things.  We call this ‘highlighting’ enhancement.  

On this basis, a group from Japan have been looking at spinal cord swelling using contrast and what it means for patients. 

What did the study measure?​
The team from Japan performed ‘contrast MRI’ scans on patients with CSM due to undergo and operation, before and after their surgery.  They then compared what happened to patients who had enhancement and those that did not have enhancement. 

What were the results?
In the study they found that those with preoperative enhancement were more likely to have developed swelling at 1 month after the operation and the swelling was more likely to persist until 1 year post operation. Those who developed swelling had poorer outcomes as assed by a scoring system called the JOA that looks at movement skills as well as sensory loss (problems with feeling). 
What does this mean for those affected?
This sort of MRI imaging is not normally performed during the work up for CSM, but the potential to offer additional information into the severity of the disease and how patients are likely to respond to surgery would be helpful to doctors and sufferers alike. 
It is worth noting that the injection of dye can be harmful to some people, although this is uncommon. 

Therefore, for this technique to be adopted, healthcare providers are likely to need further information, such as:

  1. How does this change the management of patients?  This study only looked at patients who were due to undergo an operation anyway, is spinal cord swelling present in other forms of CSM?  Can it help decide when to perform an operation?

Of course a number of additional MRI techniques are being developed, and it is possible that the information that might be provided by this method, is superseded. 

References
Ozawa et al. Spinal Cord Swelling After Surgery in Cervical Spondylotic Myelopathy: Relationship With Intramedullary Gd-DTPA Enhancement on MRI. Clin Spine Surg. 2018 May 31. doi: 10.1097/BSD.0000000000000664
Cho et al.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229731/


Can a new MRI technique predict how you respond to surgery?

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By Timothy Boerger 
Edited by Benjamin Davies

Research Summary on MRI Methods for Predicting Functional Recovery from Surgery in Patients with Cervical Myelopathy.
Rao A et al., Diffusion Tensor Imaging in a Large Longitudinal Series of Patients With Cervical Spondylotic Myelopathy Correlated With Long-Term Functional Outcome. Neurosurgery. Epub ahead of print Feb 23, 2018
Reason for the study
Currently, the assessment of the impact of cervical myelopathy is based largely on patient reported symptoms and commonly quantified using an assessment scale called the mJOA. Patient reported symptoms are very important to take into account when discussing disease severity and function, but imaging measures which explain symptoms are also helpful. Currently there has been limited success in developing imaging measures which explain symptoms and, perhaps more importantly, predict future symptoms and potential recovery following surgery. This last part will be especially important for patients and surgeons determining who will benefit from surgery. 

This study examined a different magnetic resonance imaging (MRI) technique than normal, called diffusion tensor imaging. This technique quantifies how water naturally flows (diffuses). The specific measure they chose (fractional anisotropy) measures the degree to which water flows in a single direction on a scale of 0 to 1 with values closer to 1 indicating diffusion more strongly in 1 direction. In axons of the spinal cord, for example, it would be expected that water would flow consistently along the path of axons rather than perpendicular to the axons. If a group had a worse score, however, it might indicate that they had damage to the neurons allowing water to move more freely. So, the purpose of this study to use fractional anisotropy as a measure of integrity of neurons in the spinal cord and see if this correlated with function pre-surgically and change in function following surgery.

Methods
​This study enrolled patients who were diagnosed with cervical myelopathy over a 5 year period (age range 33 – 81, 18 male, 26 female) and followed these patients for 2 years following surgery. They took their MRI scans and determined mJOA score pre-operatively. For this study they focused their imaging analysis at the spinal level with the greatest compression of the spinal cord. For this analysis they included the whole cord except for the border around the cord because the data they could gain from this area might be incorrect due to the surrounding cerebrospinal fluid. They then compared the MRI scans (fractional anisotropy) and mJOA pre-operatively, and 6-, 12-, and 24-months after surgery. They also compared fractional anisotropy values to those from a group of healthy control participants. 

Results
As expected fractional anisotropy (the MRI measure of neuron integrity) was lower in patients with cervical myelopathy than controls.  It was also associated with the severity of myelopathy before surgery, as assessed by the mJOA (a measure of patient function). 
Also, fractional anisotropy inversely predicted change in mJOA score at 12 months, but was less strongly predictive of change in mJOA at 6 and 24 months. Baseline mJOA also was inversely predictive of change in mJOA at 12 months. This means that in this study, those participants with lower fractional anisotropy (neural integrity) or mJOA (function) scores pre-operatively improved the most following surgery.

Why is this important?
At present, we are unable to predict accurately the response to surgery, and therefore markers which help this will be useful for doctors and patients.  Whilst fractional anisotropy, has been investigated before previous studies using this technique were less successful in drawing a relationship with function. This may be due to improving the methods of collecting and analyzing the MRI data. 
The identified relationship between baseline mJOA and change in mJOA with surgery are therefore promising, but require further research to understand the meaning for patients; for example it is recognized that patients with greater disability typically do improve more as measured by the mJOA, but that does not mean that they achieve a better functional outcome.The mJOA is not a linear scale, where each point gain is equally as important as the next.  
We look forward to watching our understanding of Fractional Anisotropy improve and if it can be of benefit to doctors and patients.


Broken bones more likely following a Cervical Myelopathy fall.

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By T.Boerger
Reviewed by. BM Davies

Reason for the Study
Walking impairments are a common feature of cervical myelopathy and can lead to falls.  In elderly individuals such falls, even if minor, can lead to injuries, such as broken bones.  Broken bones (‘fractures’) are more common as we get older, as aging affects bone strength, including conditions such as osteoporosis.  Such fractures generally occur in stereotyped locations such as the wrist, shoulder, hip, and low back and therefore termed ‘fragility fractures’. These secondary injuries are associated with a significant impact on life, including in some cases death.  In 2015, a group from the USA showed that 18% of patients with a hip fracture had undiagnosed myelopathy [1].  However the overall rate of fragility fractures (a fall related injury also associated with fragile bones) amongst elderly individuals with cervical myelopathy has not yet been investigated [2]


How was this study done?
This study was conducted by searching a database of Medicare patients (meaning previously collected anonymous medical data from individuals in the United States age 65+). This study included 24,439 patients with cervical myelopathy who had undergone surgery, 35,893 patients with cervical myelopathy who had not undergone surgery, and 831,532 patients without myelopathy who had a general medical appointment during the study timeframe of 2008-2011. 
For this study, the researchers excluded patients who might confuse the data (e.g. those who had a neck surgery unrelated to cervical myelopathy or history of cancer, infection, or trauma to the spine, but also those with a history of fragility fractures). The researchers then tracked the occurrence of fractures over the next 3 years and used statistical tests to account for differences in study groups which could influence the results (e.g. age, sex or diagnosis of osteoporosis). 

What did they find?
There were some differences in the characteristics of the study groups:

  1. The cervical myelopathy surgical group was more likely to be male and younger, than the non-operative cervical myelopathy group. 
  2. Both cervical myelopathy groups tended to have higher rates of additional diseases than controls
  3. The non-operative cervical myelopathy had higher rates of osteoporosis, dementia and cerebrovascular disease than the surgical cervical myelopathy group.

At 12 months follow up, both non-operative and surgical cervical myelopathy groups were more likely to sustain fragility fractures than controls. The odds ratios were 1.59 and 1.48 respectively (odds ratios indicate relative odds of a diagnosis or injury with a value closer to 1 indicating no difference). Further, the odds of fracture were higher in both groups than controls at 36 months as well, however, at 36 months the surgical group was lower than the non-operative group.

Why is this important?
There are some limitations to this study; first, because this was a search of a Medicare database it is most applicable to patients with cervical myelopathy 65 and older, but also due to the type of data recorded, there are some possible factors related to falls the researchers were unable to account for such as BMI or physical activity.
However, this is an extremely large study which gives us confidence the results are real, and not simply a coincidence.  
Hopefully these findings will help to raise the profile of myelopathy; as 1) the impact and cost of fragility fractures is significant for healthcare providers, 2) myelopathy is not routinely considered as part of managing a patient’s falls risk and 3) falls assessments are carried out by general professionals. 
Whilst surgery did not eliminate the risk of fragility fractures, they were reduced in those that had surgery.  It would appear from the characteristics of the study groups, that age and ill-health were more likely to lead to conservative management of cervical myelopathy and whether or not this is appropriate, given the potential significance of fragility fractures will need further investigation.   

​​References
[1] Radcliff et al (2015). High Incidence of Undiagnosed Cervical Myelopathy in Patients with Hip Fracture Compared to Controls. Journal of Orthopaedic Traumahttp://doi.org/10.1097/BOT.0000000000000485
[2] Horowitz JA, et al (2018). Fragility Fracture Risk in Elderly Patients with Cervical Myelopathy. Spine.
(3) Can Cervical Myelopathy cause hip fractures 

Spinal Cord Stem Cell Transplantation for Spinal Cord Injury

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By A.Willison
Reviewed by B.Davies

​Humans require many different repair and renewal strategies. At the earliest point in life, we need these pathways to grow and develop but in later life, we use these pathways to recover from disease and injury. For this, our bodies activate a unique type of cell known as a stem cell. Stem cells are a special form of cell, as they can make any cell type in the body, and so can provide building blocks for our organs and tissues.  

Over the past 20 years, researchers have been trying to harness the power of stem cells to guide damaged nerves in spinal cord injury (SCI) towards repair, or to grow new nerve cells altogether. By doing so, it is hoped that the damage can be undone, and a more effective treatment can be offered to those living with SCI. 

Recently, a Californian group led by Dr.Joseph Ciacci, has released an exciting clinical study where, for the first time in humans, four patients had a special preparation of foetal spinal cord stem cells (called Neuralstem) transplanted directly into their spinal cord at the site of injury. After following the patients’ recovery for over two years, they discovered that 3 of the 4 patients had made some improvements. Two patients recovered sensory and motor function, with a third patient showing an improvement in motor activity.  Whilst these changes were measured, it is noted that this did not lead to a change in the patient’s quality of life.  Importantly, the researchers also found no concerns about the safety or side effect profile of stem cell transplant. 

Strategies to repair the spinal cord are sorely needed, and whilst these findings must be treated with significant caution (as there was no group of patients to compare to and the improvements did not reach statistical significance), they are promising as typically for this group of patients, so far down the line after injury, no improvement would be expected. 


Much more work is required before this could lead to real world treatments, and we look forward to follow this story. 

References

  1. Curtis, E et al. 2018 A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury Cell Stem Cell  Jun 1;22(6):941-950.e6. doi: 10.1016/j.stem.2018.05.014

More to Myelopathy than meets the eye

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By O.Mowforth
Edited by B.Davies

We don’t really know what symptoms a “typical” patient with myelopathy has. 
In fact, the huge number of often quite subtle and non-specific symptoms is probably one of the main reasons why early diagnosis is so challenging (Davies et al., 2018).
 
When medical students prepare for exams they tend to learn stereotypical descriptions of conditions. For myelopathy, this might be a patient with walking problems and clumsy hands.

However, increasingly symptoms that one might never consider could be linked with myelopathy are emerging from the shadows.

Depressed or anxious mood is one such symptom (Stoffman et al., 2005). 
In recent years we have realised that myelopathy patients suffer from high levels of depressed or anxious mood and that this often improves after spinal surgery. But we have had little understanding of why this is the case.

A recent study from Japan has provided a little more insight (Sawada et al., 2018). The Japanese team studied the activity levels of various sites in the brain in myelopathy patients before and after surgery. They also studied individuals without myelopathy as a control group for comparison.
To do this, the team asked participants to do a simple finger-tapping exercise whilst they observed activity levels in the brain using functional magnetic resonance imaging.

The team found that before surgery individuals in the myelopathy group had a significantly higher activation in an area of the brain called the supplementary motor area compared to individuals in the group without myelopathy.
Next the team found that activation of brain areas, including the anterior cingulate cortex, the supplementary motor area and the thalamus significantly correlated with depression. This meant that the greater a patient’s depression, the greater the activation they had in these brain areas.  
Finally, the team found that both depression and activity in the anterior cingulate cortex and supplementary motor area decreased following surgery for myelopathy. 
Interesting!

The team argue that up to now surgeons have focussed on the “typical” symptoms such as the clumsy hands and walking problems when deciding whether to operate. They believe that their work may lead to future surgical decisions taking more account of the psychological symptoms too!

Davies, B.M., Mowforth, O.D., Smith, E.K., and Kotter, M.R. (2018). Degenerative cervical myelopathy. BMJ 360, k186.
Sawada, M., Nakae, T., Munemitsu, T., and Hojo, M. (2018). Cortical Reorganizations for Recovery from Depressive State After Spinal Decompression Surgery. World Neurosurg. 112, e632–e639.
Stoffman, M.R., Roberts, M.S., and King, J.T. (2005). Cervical spondylotic myelopathy, depression, and anxiety: a cohort analysis of 89 patients. Neurosurgery 57, 307–313; discussion 307-313.


Myelopathy Research Struggling To Gain Attention

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By Timothy Boerger
Reviewed by B.Davies

Reason for the study
The number of times a paper is cited is a common metric of how meaningful that paper is to the scientific community. Generally, papers that are highly cited have a profound impact on their field. If scientists look at the trends of which papers are most cited, it can give us an idea of what topics within a scientific discipline are experiencing the most interest over time.

Methods
The prominent journals publishing research related to the spine were first identified from a database of journals. This list of journals including: Spine, Journal of Spinal Disorders, European Spine Journal, Journal of Spinal Cord Medicine, Spinal Cord, Spine Journal, Journal of Spinal Disorders & Techniques, and Journal of Neurosurgery: Spine were searched using the database Web of Science which provides all articles ever published from the selected journals. Articles were then sorted by most citations and the top 100 cited articles were analysed. Articles were then sorted by topic including, 

  1. Biomechanics 
  2. Cervical myelopathy/Cervical fusion 
  3. Degenerative disc disease, deformity 
  4. Iliac bone graft morbidity 
  5. Low back pain 
  6. Lumbar spinal stenosis/Lumbar fusion 
  7. Neck pain 
  8. Osteoporotic compression fractures 
  9. Psychosocial aspects of neck and low back pain 
  10. Tesearch methodology 
  11. Spinal fusion/implantants and rhBMP-2
  12. Spinal metasteses (cancer)
  13. Thoracic fusion 
  14. Trauma/spinal cord injury.

Results
By far the most articles were published in the journal Spine (84/100 articles). This suggests that the journal is publishing a substantial body of the spine research which is both impactful and broadly of-interest to clinicians and researchers of spinal conditions. Ranked according to most articles by topic, low back pain was 1st and had over 2x as many articles represented as any other topic area (22/100 articles). Ranked according to most articles by topic, Cervical myelopathy/Cervical fusion was tied-9th with 3/100 articles. Of these 3, all were on operative techniques for different aspects of cervical myelopathy. The most recent of these 3 articles was published in 2001 (the other 2 were published in 1983 and 1981). Neck pain was 12th.

Why is this important?
The number of times an article was cited is often an indicator of how popular a topic is. This suggests that cervical myelopathy, despite its prevalence and impact upon a person, has received relatively little impactful research. Impactful is an important caveat here; a terrible study, or one that only marginally advances the field, will probably not receive a lot of citations in the future. This means that researchers that look at myelopathy need to produce impactful research that helps us understand mechanisms of the disease, its impact, etc. that may help drive more interest and produce more highly impactful work and better treatments.

It isn’t all doom and gloom, however. On Aug 1, 2018 I searched pubmed (another database of research articles) for all research containing the keywords

  1. cervical myelopathy 
  2. cervical Spondylotic myelopathy 
  3. degenerative cervical myelopathy 
  4. cervical laminectomy 
  5. anterior discectomy and fusion 
  6. cervical disc replacement 
  7. cervical corpectomy
  8. posterior cervical discectomy


and got 24,107 results. Similarly if you search “low back pain, one would get 34,002 results in the same database. This suggests that there is a decent amount of research compared to low back pain, but not nearly in the ball park as other disabling conditions such as multiple sclerosis (~80,000 articles). This suggests that more research is needed in all facets of the disease, but this research also needs to be well designed, rigorous, and impactful. It also means that more publicity is needed for this disease to generate more interest in the scientific community.

References

  1. Badhiwala JH et al., Highly cited works in spinal disorders: the top 100 most cited papers published in spine journals. Spine. Epub ahead of print Jun 8, 2018

Making new brain cells: how mice could help astronauts and DCM patients

By M Stewart
Editor: B Davies

It’s a commonly held belief that you can’t grow new brain cells as adult; you’re born with one hundred billion neurons and that’s as many as you’re getting. However, this isn’t quite the case. While new neurons don’t form in most parts of the human central nervous system (the brain and spinal cord), there are two special areas where new neurons do indeed arise after birth. These areas are found in specific parts of the brain with rather complicated names: the subgranular zone of the dentate gyrus  and the subventricular zone of the lateral ventricle. These two areas (which we call the ‘SGZ’ and ‘SVZ’ for short) contain what we call ‘neural stem cells’ (NSCs), which are able to produce new neurons throughout adult life. This production of new neurons from stem cells is called ‘neurogenesis’. 

Figure 1: Neurogenesis in the rodent (A) and human (B) brains. The final destinations of newly born neurons are shown in green. In both man and rodent one site is the dentate gyrus (DG). Neurons from the subventricular zone of the lateral ventricle (LV) end up in the olfactory bulb (OB) in rodents and in a part of the brain called the striatum in man. From Ernst et al 20153.

Interestingly, there’s a link between neural stem cell activity and exercise. Increased levels of physical activity have been shown to increase neurogenesis, and even restore it in mice who have stopped producing new neurons due to genetic manipulation1. Importantly, this increased neurogenesis has been associated with increased learning ability2. While we know quite a lot about what happens to neural stem cells when we move more, we don’t know much about what happens to neurogenesis when we move less. This gap in our knowledge actually rather important when we consider that prolonged reductions in movement are increasingly common. Lack of muscle activity occurs inn prolonged bed rest or neurological diseases which affect motor function, like spinal cord injury, multiple sclerosis or potentially DCM. Alternatively, effects equivalent to reduced movement can occur in prolonged stays in space, where there the reduced gravity means that muscles aren’t placed under load. 

As patients survive longer with neurological diseases and as we expect longer stays in space, it becomes more and more important to understand any links between immobility and neurogenesis for two reasons. Firstly, changes to neurogenesis could affect brain health – it may be that changes to neural stem cells following reduced mobility feed back into disease like MS or DCM and actually become part of the cause. Adult neurogenesis is greatly decreased in Huntington’s disease patients when compared to healthy people, suggesting that there could be a link between reduced neurogenesis may play a role in the disease3. Secondly, exploring the link may help us understand the effects of exercise on the brain. Reduced movement has been shown to impair memory function and learning4 and to change the chemical environment of the brain5. We may also be able to better understand the link between exercise and prevention of neurodegenerative conditions like Alzheimer’s disease, which is associated with degeneration in neurogenic areas6.

For all the above reasons, a team from Italy lead by Rafaella Adami recently set out to explore whether reduced movement lead to changes in neural stem cells7.
The study was done in mice. While mice do have some notable differences to humans in terms of the neural stem cells (see below), these experiments require the dissection of large amounts of brain tissue and immediately after death and so are practically impossible to do in humans. 

PictureFigure 2: Diagram of the HU mouse model. From Barbosa et al 20118

How was this study done?
The researchers wanted to recreate the conditions seen in situations (e.g. neurological diseases) where people can’t move very much. In these situations limbs are ‘unloaded’ – people aren’t using their arms or legs to move their weight around. in something called the ‘hindlimb unloading model’8 (HU) mouse model. Mice are suspended by their tales from the ceiling of a cage, taking the load off their hind legs, but leaving them free to walk on their front legs. Thus the hind legs don’t bear the mouse’s weight and are ‘unloaded’ (see figure 2). Adami et al put a group of mice in this position for 14 days, over which time their back leg muscles shrank significantly, as they would if they were unable to move them due to neurological disease (or if they were in space and carrying no weight!). After 14 days the mice were killed and their brains where dissected to examine the neural stem cells in the SVZ. Brains from mice which had been allowed to run around their cages freely where used for comparison (control). 

It’s important to stress that the mice were well looked after during the experiment. They always had access to as much food and water as the wanted and were visited by a vet 3 times during the 14 days of suspension. The showed the same key mouse behaviours as the free (control) mice and showed no increased levels of stress hormones. Taken together, all these factors strongly suggest that the mice suffered “little” stress during the experiment.

What were the results of the study?
Firstly the researchers looked at the number of proliferating (dviding/reproducing) cells found in the SVZ. In this case, proliferating cells were the stem cells that were dividing to make neurons, so more proliferation suggests more neurogenesis. Adami et al found that there were 70% fewer proliferating cells in the HU mice compared to controls – so neurogenesis was reduced. 

The team then wondered if this reduced proliferation meant that the stem cells themselves had changed in some way. To explore this possibility, they then took NSCs out of the HU and control mouse brains and grew them in a dish, to form a ball of stem cells and neurons. They saw that stem cells from HU mice divded more slowly than in controls, taking 7 days to double in number (the controls only took 2 days). They also checked that this slower rate of growth wasn’t due to cells dying.

Overall, these findings led the team to their first key result: reducing movement reduces the proliferative capacity of neural stem cells. 
Adami et al then wondered what caused this reduced proliferation. They discovered that it was because the more of the HU mouse stem cells appeared to have become stuck in the ‘resting state’ when compared to the control mouse stem cells. 69%  of HU stem cells were found to be in a resting state, compared to 57% of controls. Far more of the control cells were in a very active, dividing state (21% vs 13% of HU mice).
The researchers then looked at whether the neural stem cells were able to form mature neurons. They found that 6.8% of control stem cells could form mature neurons, whereas only 0.5% of HU stem cells could. 

This lead the team to their second key result: reducing movement reduces the maturation capabilities of neural stem cells. 
Next, Adami  et al explored whether the metabolism (energy production) of neural stem cells in HU mice had changed. Most neural stem cells produce energy by a process called glycolysis, which by produces a byproduct known as lactate. HU stem cells produced significantly less lactate than controls cells, suggesting that reduced movement gives neural stem cells an abnormal metabolism. 

Finally, to try and understand what could be underlying these changes, the researchers looked at gene expression in the neural stem cells. They found that expression of 2 genes were significantly different between HU and control samples. A gene known as CDKrap1 was 3.5x lower in HU stem cells than in controls, while a gene known as cdk6 was 2.3x high in HU stem cells. Overall, it appears that reduced movement changes the genes expressed in neural stem cells. Adami et al haven’t commented on what these different levels of cdkrap5 might mean, but they think that the higher levels of cdk6, which helps keep cells in the resting state rather than dividing, could explain the reduced neurogenesis seen in HU mice.

What do these results mean for DCM?
Right now, not a great deal. This work is still very much ‘blue sky research’ intended to see if the neural stem cells are worth further study for neurological disease (or space travel!). While its fascinating to see that that restricting movement leads to change in neural stem, we have to be cautious in how far we extrapolate the results to humans. Firstly, while mice and humans may be similar, they aren’t the same (newly born neurons rom the SVZ actually end up in a totally different places in mice and people). Secondly, while DCM can involve reduction in movement if nerve damage progresses to an extreme stage or pain becomes debilitating, it’s not quite as clear cut as in this mouse model. Therefore it’s hard to say if neural stem cells would undergo the same changes in DCM patients as they do here. Thirdly, it’s difficult to understand the implications of the results when we don’t fully understand how/if reduced neurogenesis contributes to neurological diseases. Furthermore, the consequences of reduced neurogenesis are likely to vary across conditions – changes to neurogenesis might be completely in DCM than they are for something like Huntington’s. 
The next step will be to explore the nature of neural stem cells in other mouse models of reduced movement, such as multiple sclerosis, spinal cord injury and DCM to see if neural stem cells undergo similar reductions in neurogenesis. Then we’ll need to determine how/if reduced neurogenesis might contribute to the problems we see in these conditions. If such a contribution was confirmed, this could be a breakthrough in our understanding of how DCM develops. We might even then be able to developing new treatments which target the neural stem cells themselves. However, there are many steps we must take before we reach that stage – for now we’ll have to move slowly. Watch this space for more!


1.    Farioli-Vecchioli, S. et al. Running Rescues Defective Adult Neurogenesis by Shortening the Length of the Cell Cycle of Neural Stem and Progenitor Cells. Stem Cells 32, 1968–1982 (2014).
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3.    Ernst, A. & Frisén, J. Adult Neurogenesis in Humans- Common and Unique Traits in Mammals. PLOS Biol. 13, e1002045 (2015).
4.    Wang, T. et al. iTRAQ-based proteomics analysis of hippocampus in spatial memory deficiency rats induced by simulated microgravity. J. Proteomics 160, 64–73 (2017).
5.    Dupont, E., Canu, M.-H., Stevens, L. & Falempin, M. Effects of a 14-day period of hindpaw sensory restriction on mRNA and protein levels of NGF and BDNF in the hindpaw primary somatosensory cortex. Brain Res. Mol. Brain Res. 133, 78–86 (2005).
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