Cerebral palsy

Clearing the air

Every so often I’m asked about why we tend to do clinical gait analysis barefoot and in AFOs (and shoes). One answer is that the barefoot condition tends to give a better indication of the full extent of a patient’s problems whereas walking in AFOs may be a better indication of how they function in everyday life. Another, however, is that sometimes walking in AFOs can help in identifying which particular impairments are having the most effect on gait. This was certainly the case when, a couple of weeks ago, I was reviewing one of the case studies we often use for teaching purposes but which exhibited features that I had not previously understood.

The analysis is of a seven year old girl with diplegic cerebral palsy (GMFCS III). She can take a few steps unaided but normally walks with a K-walker. We actually tested her in and out of the K-walker barefoot and in shoes and AFOs. the K-walker didn’t make that much difference to the kinematics with either condition so we’ll focus on the two unassisted walking conditions.

toe-walking-graphs

Perhaps the most obvious feature of the barefoot data is that she walks right up on her toes in considerable plantarflexion (feature c). The physical examination data shows that plantarflexor contractures (no passive dorsiflexion with knees extended beyond 10° plantarflexion ) can account for some of this but there are also signs of spasticity (from modified Tardieu and Ashworth tests). There is also, however, some suggestion of late (feature b) and reduced (feature a) knee flexion in swing. There is no clear explanation of this from the physical exam although there is a response to the Duncan-Ely test when performed quickly which might indicate some rectus femoris spasticity. Along with these specific findings the assessment indicates generalised weakness, persistent bilateral femoral neck anteversion and some mild tightness of the hip flexors.

The gait analysis with AFOs is quite different. The solid AFOs cast in a neutral position (which might have been assumed to be too aggressive given the physical examination) do appear to be holding the ankle in neutral  and substantially limit movement at the ankle (feature h).  The pelvis is a little more anteriorly tilted (feature d), possibly to move the centre of mass anteriorly as the new sagittal plane foot alignment will move the centre of pressure anteriorly (the steps were too short to get reliable kinetics). This would also exert a greater external extending moment at the knee which accounts for the hyperextension in late stance (feature g). The increased pelvic tilt leads to increased maximum hip flexion whereas the hyperextension pushes the knee back and maintains maximum peak hip extension. The overall effect is an increased range of movement at the hip (feature e). Perhaps most interestingly though, given that there is a question as to whether the rectus is spastic or not, is that peak knee flexion in swing is essentially normal (feature f). The slope of the knee graph through toe off is if anything a little steeper than normal. Such free flexion of the knee suggests that rectus spasticity is not a problem. Peak knee flexion is still delayed but this is clearly seen to be a consequence of the knee being too extended as it starts to flex in middle single support rather than of any stiffness. In summary, the data from the barefoot condition is inconclusive as to whether rectus femoris spasticity is contributing to the gait pattern but the data from the AFO condition provides quite strong evidence that it is not.

I hope that this has answered the question I posed at the beginning of this post but it does prompt another question – if there is no rectus spasticity then why is peak knee flexion so reduced in the barefoot condition?

I think the answer to this may lie in the observation that if a person is walking on their toes (and in plantarflexion) then it actually requires considerably less knee flexion for clearance in swing than in normal walking. In other words this girl may be showing reduced knee flexion in swing simply because she doesn’t need it when walking barefoot not because there is anything wrong with her knee function.In AFOs the ankle is held in neutral which makes clearance much more difficult and she has no option but to flex the knee more. It is interesting to note that when walking with shoes and AFOs she walks 20% slower than in bare feet and looks considerably less stable and fluent in her movements.

Rather than waste a lot of text in trying to explain why this occurs I’ve recorded a short video using Verne to illustrate that this is the case.

I go into the underlying concepts in relation to normal gait in this screen cast and have explored some of the other consequences of this for those walking in a more crouched gait pattern in this video blog.

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Sense of satisfaction

Modern academic research is largely a rather slow process taking small incremental steps. I’ve vented my frustration before about how dispiriting it can be to get lost in a fog of low-level research projects which often leave us more confused rather than enlightened. I thus feel I want to celebrate a rare occasion when I do feel a sense of completion of a substantial programme of research.

I was lucky enough to move to Belfast  shortly after Kerr Graham and Aidan Cosgrove  had completed their early work demonstrating the efficacy of Botulinum toxin injections first in hereditary spastic mice and then in children with cerebral palsy. Kerr had departed for Melbourne by the time I arrived but left Niall Eames, an orthopaedic surgeon, lined up to do some research to try and better understand the effect of the toxin. Given that the problem in CP is that the muscles are too short and that Botulinum toxin, by reducing the neural input to the muscle, allows them to elongate, we decided that we should do this by looking at the changes in muscle length. We thus started with some, by modern standards extremely crude, muscle length modelling of the gastrocnemius.

Niall graph

Response to botulinum toxin plotted against the pre-operative dynamic component (taken from Eames et al. 1999)

Having developed the model we applied it to a cohort of children with cerebral palsy having Botulinum toxin injections and were able to demonstrate that the action of the toxin was to reduce the “dynamic component” of reduced muscle length (see figure above). This makes a lot of sense as it is this component that is affected by the neural input to the muscle. The “fixed component” (contracture) is largely a consequence of changes to the composition and structure of the muscle and is unlikely to be affected by the toxin. The research also allowed us to understand that the variable response was largely due to children having a different dynamic component rather than of the toxin acting differently and led to reasonably simple prescription guidelines. Botulinum injections to the calf are most likely to be beneficial if the child has a large dynamic component (good range of passive dorsiflexion during physical examination but walking up on their toes). It further explained that the different response in children with diplegia  and hemiplegia was also attributable to them having different magnitudes of dynamic component.

Armed with this understanding I was then able to work with the pharmaceutical company Ipsen to set up a cliniucal trail to establish the most appropriate dose of the toxin. We couldn’t find enough children to study in the UK so had to extend the study to five centres in Poland. We divided children into one of four groups and injected them with either a placebo or one of three different doses. We used the same modelling technique which we had developed for the earlier study to analyse the results and came to  the conclusion that placebo didn’t work (very much) and that the middle dose was the most effective (see figure below). It was interesting that the biomechanical modelling came to clear logical conclusions whereas doctors’ subjective opinions were that the placebo was very nearly as effective as the drug and that they were so impressed by the “improvement” after placebo injection that they would have recommended repeating the process for two thirds of the children! (despite biomechanical evidence that the placebo had had no effect).

Baker graph

Reduction in dynamic component as a function of different doses of Botulinum toxin at 4, 8 and 16 weeks (Baker et al. 2002)

Having established the most appropriate dose on a single occasion the most obvious remaining question is, “How often should those injections be repeated?”. I’d moved to Melbourne to join Kerr by then and we applied to the Australian National Health and Research Council to fund a clinical trial to compare injections delivered either annually or every four months over a  two year period. Reflecting on the biomechanics we recognised that the long term goal of the injections had more to do with preventing the development of secondary fixed contractures than on the immediate effect on the dynamic component. We would have to measure relatively small changes over a two year time span and thus devised a method to standardise the measurement of passive dorsiflexion range as much as possible.

Which brings me to the stimulus for writing this post in that the results of that study have just been published . The first conclusion is that passive range of dorsiflexion was maintained over the two year period by both injection regimes. We had no true control, because by this stage it wasn’t considered ethical to inject placebo over such a long period, but these measurements were taken over an age range in a child’s life during which preserving dorsiflexion range would be extremely unlikely without injections. The second conclusion was that the more regular injections where only slightly more effective in preserving dorsiflexion range and therefore that there doesn’t appear to be any particular benefit in injecting more regularly than once a year.

Thus after nearly twenty years of research based on the application of thoughtful biomechanics to a clinical problem we finally have clear evidence of which children to inject, how much toxin to inject and how often to repeat this. As one leader of the western world was once heard to comment under less auspicious circumstances, “Mission accomplished!”

Footnote

Trials like this take so long to organise that we were not actually the first group to complete a study to establish the most appropriate injection frequency. This was actually published about 5 years ago. It was a very similar study (it had been sponsored by Ipsen as a follow-on our to earlier work and I’d had some involvement in its planning before I left for Australia) and arrived at a very similar result. Rather than feeling that there was competition here though it highlights the scientific importance of repeating studies to confirm results. With such an emphasis on innovation in modern clinical research the need to repeat and confirm earlier results, which is an important part of the scientific process, can very often be overlooked.

 

Feeling the pressure

I’ve been quite techie in my posts recently so maybe its time for something more clinical. I received a request from a journalist with the popular science magazine “New Scientist” to comment on an article (Mukherjee et al, 2014) reporting on research purporting to provide evidence of the efficacy of hyperbaric oxygen therapy for children with cerebral palsy.

Such articles “discovering” new treatments for cerebral palsy appear every so often. The last time hyperbaric oxygen was discovered was just over a decade ago. At the time a number of centres throughout the UK, Europe and Australia started offering the treatment and many parents sought these out. The fact that this interest appears to have largely died away I think speaks for itself.

Despite its claims the article is published in Undersea and Hyperbaric Medicine Journal. This suggests to me that it has either been rejected from mainstream journals in the cerebral palsy field or that the authors have chosen not to submit it for the rigorous peer review that this would entail. Assuming that it has been reviewed and assessed as lacking credibility I looked at the article myself.

The article is actually well written with the authors being particularly honest in highlighting several limitations. The most obvious is that this is not a randomised trial. The control group were those children with parents who did not want hyperbaric treatment for some reason.  This group is much smaller than the other groups and contains a higher proportion of more severely involved children (quadriplegia) than two of the other groups. The authors also accept that there was no blinding of clinicians, families or assessors.

The other obvious issue is that all children were also undergoing an intense rehabilitation programme over a six month period of the study whereas the hyperbaric oxygen was only offered over the first two months. The similarity between the three treatment groups is remarkable despite marked differences in the hyperbaric oxygen regime. The lowest dose of hyperbaric oxygen is actually one of hyperbaric air. The other doses are of pure oxygen (5 x more oxygen) at considerably higher pressures. I’m no expert in hyperbaric medicine but if the hyperbaric regime is the important factor here I’m surprised that such marked differences between regimes make so little difference to the results (summarised in Figure 1).

Mukherjee Fig 1

The improvement appears to continue throughout the treatment period and not just over the early period when hyperbaric oxygen was being used.  Given that the differences between control and hyperbaric oxygen might be attributed to some inherent bias in selecting the controls, the most direct explanation of the data would appear to me to be that the common rehabilitation programme is responsible for change rather than the different hyperbaric oxygen regimes.

Mukherjee Fig 2

The improvements in GMFM appear large particularly as plotted against the GMFM “growth curves” in Figure 2. There are, however, also issues here. Comparison of the age range and means of all treatment groups suggests a highly skewed distribution with a large number of very young children and a small number of adolescents. The mean value is almost certainly a poor indicator of central tendency and the median should have been used which will almost certainly be considerably lower. You can see that if the age at which the lines in Figure 2 are plotted where reduced by just one year then the improvements over six months would be much closer to those expected on the basis of the growth curves. The early years of childhood are a time of rapid development of motor function in all children, including those with cerebral palsy, and particular care is needed to take this into account while quantifying the effect of specific interventions at this age.

The other issue here is that the growth curves are based on data from Canadian children attending established ambulatory rehabilitation programmes on an on-going basis. If the children in the hyperbaric oxygen study had been less well managed before being recruited then the rapid gains on starting such a comprehensive rehabilitation programme for the first time may not be that surprising.

The acknowledgements list also makes interesting reading in that it is suggests that there are a considerable number of stakeholders in this project. I could imagine that providing evidence for the efficacy of this treatment could be extremely important for its future. In the light of this I’m not convinced by the final statement that “the authors report that no conflict of interest exists with this submission”. (Of course this merely highlights implicit conflicts of interest in almost everything that is published in the scientific literature and it may be a little unfair to make this criticism of this study and not of others).

In summary it appears quite clear to me why mainstream journals might have been reluctant to publish such a study and I’d think it extremely unlikely that this is the break through that it might appear at first site.

If the paper has been declined by the mainstream CP journals then it is interesting to reflect on whether this has been “successful” or not. The paper is well written and appears to report results of an observational study that has been conducted at least as rigorously as many others that are routinely accepted by such journals. The authors have been particularly honest in reporting the limitations of the study. The explanations as to why the results may not be as sensational as first appears are quite subtle and I’m not particularly surprised that they have been over-looked by authors who (like most of us when we publish) want to place a particular spin on their results.

If the article had been accepted then the journal editors could have asked the authors to revise their manuscript to draw more balanced conclusions or could have included an editorial emphasizing an alternative point of view. I think it unlikely that the popular scientific press would have raised an eyebrow.  Instead the article has appeared in a journal dedicated to hyperbaric medicine with an editorial written by protagonists for this “new” therapy who conclude that it “could be the coveted neurotherapeutic method for children suffering from neurological dysfunctions due to CP”. I’m not convinced that this is a good result for the CP community who I think have enough to contend without the publicity that occasional reports of such “wonder cures” gives rise to.

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Mukherjee A, Raison M, Sahni T, Arya A, Lambert J, Marois P, James PB, Parent A, Ballaz L (2014). Intensive rehabilitation combined with HBO2 therapy in children with cerebral palsy: a controlled longitudinal study. Undersea and Hyperbaric Medicine Journal 41(2):77-85.

 

The advantages of crouch gait?

Thought I’d try a video blog for a change to show you how I’ve been using e-Verne to explore the kinematics of crouch gait with some counter-intuitive findings.

If you want to learn more you can skip to my YouTube screencast on what determines adequate step length and another one on how clearance is achieved (or go to my YouTube channel).

Why bother with gait classification?

There is a sector of our community that sees classification as the holy grail of gait analysis. If only we could divide our patients into neat little categories then our problems will be solved. But why do we want to classify patients?

The most obvious reason for categorising patients into groups would be if genuinely different groups existed. But do they? In an earlier blog I’ve written about the GMFCS and pointed out that there is absolutely no reason to believe that children with cerebral palsy fall into distinct categories of severity – they almost certainly lie on a continuous spectrum.  I suspect that the same is true of gait patterns. Indeed in work that Fiona Dobson completed for her PhD thesis but never published we used a technique called multi-dimensional scaling to look for evidence of clustering of gait patterns in children with hemiplegic cerebral palsy. We couldn’t find any. Whichever way we looked at the data it looked like a random scatterplot.

So if there is so little evidence that gait patterns fall into distinct categories why are we so obsessed by it?

I suspect that classification systems are assumed to help clinicians – particularly less specialist ones than are employed in our gait analysis services. If we can simplify understanding of gait to a small number of discrete categories then we’ll be able to teach people to recognise these. If we can describe management plans for the different categories then maybe we can even teach people to treat the patients.

There are problems though.  The first one is that the classification systems don’t seem to work – clinicians can’t agree on what category a gait pattern should be placed in. Fiona Dobson, in one of the few studies to assess reliability of a classification in a centre outside that in which it was developed (Dobson et al,2007), looked at the agreement of 16 clinicians in rating gait patterns of 34 children with hemiplegic cerebral palsy . On the basis of video data, only one pattern was put in the same category by all clinicians and in over a third there was less than 50% agreement. An important feature of this study was that the 16 clinicians were all specialists in gait analysis of children with cerebral palsy. What would the results have been like if the non-specialist clinicians, who presumably have most to gain from classification systems, had been recruited to the study? Results were a little better when gait analysis data was used as a basis for classification, but then the clinicians for whom classification is likely to be most useful don’t generally have access to gait analysis.

Another issue is that gait patterns are almost certainly a combination of characteristics of the child and of how they have been managed previously. The Winters, Gage and Hicks (1987) classification of hemiplegia intentionally excluded children who had had previous surgery but the classification of diplegia by Rodda et al. (2004) included children with prior calf surgery (because there were so many of them). We never quantified it but it appeared to us that fewer and fewer children in Melbourne fell into the Rodda “crouch” category over time which we attributed to more conservative early surgical management and the wider use of Botulinum toxin. If this is the case then classifications schemes will have to be sufficiently generalizable to cover the effects of different management practices or maybe we need a number of different classification schemes depending on different management practices in different parts of the world.

Developing and validating classification schemes is a considerable undertaking. Earlier schemes were generally based on the enlightened but essentially subjective opinions of leading clinicians. In an era of evidence-based practice this is no longer satisfactory and widespread consultative processes (such as a Delphi process) would now be needed to convince the clinical community of any new scheme.  Similarly were existing schemes have been validated this has tended to be on the basis of repeatability studies based within the teams who developed the scales and typically using gait analysis techniques that may not be available to those who are most likely to benefit from the classification. Convincing validation of new schemes will need to be more comprehensive. Such an investment of time and effort would be perfectly justified if we are certain that the schemes will be useful – but we do need to be certain.

Validation is made considerably more complex by the fact that the classification systems do not fit the underlying reality. How can you interpret reliability studies designed to test the competence of clinicians to ascribe gait patterns to categories when there is genuine ambiguity in whether any individual child actually fits a particular category? A similar issue arises with the usefulness of the scheme for less experienced clinicians. Many children will either be on the borderline of categories or may not fit cleanly into categories at all. Explaining how to deal with such exceptions to generalist staff may lead to more confusion not less.

So is there an alternative? Well I’d like to float the potential of what I call profiling. Rather than select a number of discrete groups into which gait patterns can be assigned we define aspects of the gait pattern that vary across the patient population. We can then score or grade the different aspects separately. This allows us to accept that there is a continuous distribution of gait patterns and that also that gait might vary independently across the different aspects rather than suggesting that there is necessarily grouping of the aspects as is required by classification schemes.

We presented a paper proposing this for the gait of children with hemiplegic cerebral palsy at the Sydney CP meeting in 2008 (Tirosh, Dobson et al.) but never took the ideas any further. A factor analysis based on movement analysis profile scores suggested that 85% of the variability could be explained by 5 factors which reflected:

  • distal sagittal plane features (knee flexion and ankle plantarflexion combined),
  • leg length discrepancy (anatomical and functional),
  • hip rotation,
  • hip flexion
  • foot alignment.

These factors all make clinical sense as does the idea that hemiplegic gait should be categorised by assessing how far each of these different aspects contributes to the gait pattern of an individual child rather than trying to assign the gait pattern to one of a small number of categories. Perhaps more importantly it appears to me (and I admit this is a subjective opinion) that the underlying model of gait patterns varying along a continuum in a number of different dimensions matches reality more closer than a model assuming that gait patterns fall into distinct and recognisable categories.

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Dobson, F., Morris, M. E., Baker, R., & Graham, H. K. (2007). Gait classification in children with cerebral palsy: a systematic review. Gait and Posture, 25(1), 140-152.

Rodda, J. M., Graham, H. K., Carson, L., Galea, M. P., & Wolfe, R. (2004). Sagittal gait patterns in spastic diplegia. Journal of Bone and Joint Surgery. British Volume, 86(2), 251-258.

Winters, T. F., Jr., Gage, J. R., & Hicks, R. (1987). Gait patterns in spastic hemiplegia in children and young adults. Journal of bone and Joint Surgery – American, 69(3), 437-441.