Cerebral palsy

The importance of objective outcome measurements

This post was stimulated by a presentation given to the GCMAS by Nancy Lennon of the A.I. Du Pont Hospital in Delaware. She presented data on measured activity levels over the year following major orthopaedic surgery for children with cerebral palsy. Her data came from a case study and showed how the patient’s activity levels fell markedly at 3 months after surgery before picking up through the rest of the post-operative year.

The graph below is an update of one I prepared for a lecture on Outcome Measures at the Melbourne Gait Courses last year. It puts together data from a range of sources to suggest a time history for the Gross Motor Function Measure (GMFM, Russell et al., 1989)  for a child with cerebral palsy who has single event multi-level surgery (SEMLS) at the age of 10. The data points are taken from Thomason et al (2013) and represent average GMFM scores for a cohort of children at baseline (blue) and 12, 24 and 60 months (green) following SEMLS.  Before surgery I’ve assumed that the data follows the latest GMFM curves (Hanna et al., 2009) to arrive at the baseline value.

GMFM

The red point is invented. It is an estimate of the GMFM a child might record if assessed on coming round after surgery in a hospital bed with below knee casts. The actual value is not particularly important but seems reasonable when I glance through the GMFM manual. I’ve then extrapolated the curve from this point through 12, 24 and 60 month data points.  Having seen the videos of kids coming back for 3, 6 and 9 month follow-up after such surgery whilst in Melbourne I don’t think the time course over the first year is too far away from reality. I’ve finished off the curve assuming that it follows the known GMFM data (Hana et al., 2009).

First thing to point out is that average GMFM score at one year is almost exactly the same as at baseline and the maximum GMFM is recorded at two years following surgery suggesting that the one year follow-up may be a little early to assess outcomes.

The point I really want to make though is that if you look at this graph the biggest feature is not the improvement from pre-op to 12 or 24 month status. It is the drop in function immediately after surgery and the improvement back to baseline at 12 months. This has the potential to impact on patient, family and clinical perceptions of outcomes. If the dominant memory of the surgery is of the condition the child was in immediately afterwards, then the perception may well be of the change following surgery as being represented by the difference between the green points and the red point which might lead to a much more positive view of outcomes than a more scientific comparison with the blue point. Particular caution may have to be exercised in interpreting the results of subjective or semi-subjective assessments such as heath related quality of life questionnaires or informal assessment of outcomes.

Final point is that there are a multitude of reasons for performing such surgery and assessing outcomes on the basis of any one measure in isolation is inappropriate. I’ve plotted this data to make a particular point about the time course of recovery not to make any general conclusions about the effectiveness of the surgery. Gait Profile Scores (Baker et al., 2009) reflecting the quality of the gait pattern improved by over 30% in the same cohort for example.

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Russell, D. J., Rosenbaum, P. L., Cadman, D. T., Gowland, C., Hardy, S., & Jarvis, S. (1989). The Gross Motor Function Measure: a means to evaluate the effects of physical therapy. Developmental Medicine and Child Neurology, 31(3), 341-352.

Thomason, P., Selber, P., & Graham, H. K. (2013). Single Event Multilevel Surgery in children with bilateral spastic cerebral palsy: a 5 year prospective cohort study. Gait Posture, 37(1), 23-28.

Hanna, S. E., Rosenbaum, P. L., Bartlett, D. J., Palisano, R. J., Walter, S. D., Avery, L., & Russell, D. J. (2009). Stability and decline in gross motor function among children and youth with cerebral palsy aged 2 to 21 years. Dev Med Child Neurol, 51(4), 295-302.

Baker, R., McGinley, J. L., Schwartz, M. H., Beynon, S., Rozumalski, A., Graham, H. K., & Tirosh, O. (2009). The gait profile score and movement analysis profile. Gait Posture, 30(3), 265-269.

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Averaging up the profits

Here are two graphs. The first from very early in my career shows a parameter we called the “dynamic component” of gastrocnemius length. It plots the improvement in this after injection of botulinum toxin in children with cerebral palsy against the baseline score (Eames et al., 1999). I remember when Niall first showed me the graph. We’d captured a  whole load of data on these kids and were wondering what to plot to make sense of it. This was the first suggestion and I can still remember Niall’s excitement when it came up with such a strong relationship.

Eames

At the other end of my career here’s another graph from a paper that has only just been published electronically in Gait and Posture (Rutz et al. 2013). Here is the improvement in Gait Profile Score (GPS, Baker et al., 2009) for children with cerebral palsy plotted against baseline score (with GMFCS II and III children plotted separately). Again there is a strong correlation. (There are some statistical issues in plotting data this way which might lead to exaggeration of the correlation when measurement error is substantial but I’ve gone to some lengths in the recent paper to show that this is unlikely.)

rutz

When you think about it though the relationship is actually quite unremarkable. What both studies are showing is that kids with the most severe problems to start with are the most likely to show improvements. To a certain extent this is common sense – if two kids both improve by 30% then the child with the biggest problem to start with will show the biggest change in absolute units.

What interests me though is that if we only look at the average changes in each group we will reach the conclusion that the group as a whole have improved. If we are not careful we might conclude that all the group has improved. Thissimply isn’t the case. The full truth is that the kids who have the biggest problems have improved a lot those with milder problems haven’t improved very much (in absolute terms).

The Botulinum toxin study became the basis for an industry sponsored randomised controlled trial (Baker et al. , 2002). In that trial although we included baseline readings as a covariate in the statistical analysis but we only ever reported group results. That is still probably the most rigorous trials of lower limb injection of Botulinum Toxin in the literature. The message that almost everyone has taken out of that study  from the data we presented is that kids with spastic diplegia will benefit form Botulinum toxin. Had we presented the data more carefully the conclusion should have been that the more severely affected kids will benefit from Botulinum Toxin big time, but that  the milder kids may not benefit at all.

As it stands the paper is really convenient for the company because it suggests that a wider group of kids will benefit from an expensive drug than is actually the case. Given that bigger responses to treatment in more severely affected people is likely in almost all conditions that affect people across a range of severity I suspect that a similar phenomena spread across almost all of . I wonder how much profit the drug companies are making as a consequence?

Leave a comment or double click “n comments” link at top of post to view discussion.

Baker, R., Jasinski, M., Maciag-Tymecka, I., Michalowska-Mrozek, J., Bonikowski, M., Carr, L., . . . Cosgrove, A. (2002). Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study. Dev Med Child Neurol, 44(10), 666-675.

Baker, R., McGinley, J. L., Schwartz, M. H., Beynon, S., Rozumalski, A., Graham, H. K., & Tirosh, O. (2009). The gait profile score and movement analysis profile. Gait Posture, 30(3), 265-269.

Eames, N. W. A., Baker, R., Hill, N., Graham, K., Taylor, T., & Cosgrove, A. (1999). The effect of botulinum toxin A on gastrocnemius length: magnitude and duration of response. Dev Med Child Neurol, 41(4), 226-232.

Rutz, E., Donath, S., Tirosh, O., Graham, H.K., Baker, R. (2003). Explaining the variability improvements in gait quality as a result of single event multi-level surgery in cerebral palsy. Gait Posture, published on-line http://dx.doi.org/10.1016/j.gaitpost.2013.01.014

Little boxes

GMFCS  is a categorical scale (Palisano et al., 1997, 2008). Children and adolescents are allocated to one group or another. There’s absolutely no evidence, of course, that there is anything in the condition (or group of conditions) we call cerebral palsy to suggest that children’s gross motor abilities are distributed in such neat little packages. The spectrum of cerebral palsy is almost certainly a continuum and the gross motor abilities are almost certainly distributed along a continuum as well. The categories of the GMFCS do not represent actual discrete groups of children with gross motor abilities that are qualitatively different from those in the other groups. Rather, they are an administrative convenience. Medicine, and life in general, is littered with examples of continuously distributed parameters divided into essentially arbitrary categories simply because this is the easiest thing to do.

Bill Reid's depiction of GMFCS II (ROyal Children's Hospital, Melbourne)

Bill Reid’s depiction of GMFCS II (Royal Children’s Hospital, Melbourne)

Remembering this is important when we engage in discussion about how clearly children can be allocated to the different categories and also how stable that categorisation is over time. If the classification is actually a convenient division of a continuous spectrum then there will be a number of children who fall very close to the border line between these  groups. Some of them will lie sufficiently close to the boundary that they can’t be reliably categorised. One day they will illustrate the characteristics of one group and another day the characteristics of another. Alternatively one assessor will make a subjective decision to put the marginal patient in one group whereas another assessor will put them in the other group. Neither is wrong – it is just a consequence of taking people on a continuum and trying to put them in boxes. Just how many children inhabit this marginal space is unclear but in assessing the reliability of the classification system we should be anticipating at least some borderline children for whom it is not possible to allocate a definitive GMFCS level. I may not have been reading carefully enough but I’ve never seen any discussion of this in the relevant literature.

This also impacts on studies of stability of the GMFCS over time. We should expect that a fairly modest improvement in gross motor function should take a child who has been graded at the top end of one category at one time to lead them to be graded at the lower end of the next category up on a later occasion. Equally we should expect some children at the lower range of ability for any given range to drop a level if they deteriorate quite mildy. Some transition between neighbouring groups is thus an inevitable consequence of how the groups are defined and should be expected.

 

Palisano, R., Rosenbaum, P., Walter, S., Russell, D., Wood, E., & Galuppi, B. (1997). Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol, 39(4), 214-223.

Palisano, R. J., Rosenbaum, P., Bartlett, D., & Livingston, M. H. (2008). Content validity of the expanded and revised Gross Motor Function Classification System. Dev Med Child Neurol, 50(10), 744-750.

GMFCS based research -are we asking the right questions?

It’s fifteen years since the publication of the first paper on the GMFCS (Palisano et al., 1997). Since then it has become ubiquitous in the field of cerebral palsy. More and more measures are being found that correlate with it. It just seems like magic. But the more things we discover that show this correlation the more I wonder whether this really is magic. Have we missed something? Are we asking the right questions?

Cerebral palsy is an extremely heterogeneous condition affecting some kids extremely severely and others very mildly. In terms of gross motor function the range is from a child with  hemiplegia and a mild foot drop right through to those with severe total body involvement who are essentially immobile. GMFCS allows us to group children (and now adolescents, Palisano et al., 2008) in terms of that function. In other words, GMFCS is essentially a classification of the severity of CP as indicated by gross motor function.

When we think about it most of the other indices, scores and scales we look at can be considered to be measures of the severity of CP as indicated by other aspects of the condition. When we get a correlation between GMFCS and another measure we are thus really saying there is a correlation of the severity of CP indicated on the basis of Gross Motor Function and severity of CP as indicated by hip dysplasia (Robin et al., 2008, see Figure below) , or gait quality (Baker et al., 2009) or physical activity (Bjornson et al., 2007). We shouldn’t really be surprised that there is a correlation – in fact the thing that should really surprise us is if there isn’t.

GMFCS-MP

Correlation of hip dysplasia (migration percentage) with GMFCS (Robin et al., 2008)

A more nuanced approach to research in CP might be to anticipate the underlying correlation between indicators of severity of CP and accept it as unremarkable. Measures that don’t correlate are actually more remarkable and further investigation of these, when they are identified, might be more productive than investigation of those that do. Detailed consideration of individual children that buck the trends may also give important clinical insights.

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Baker, R., McGinley, J. L., Schwartz, M. H., Beynon, S., Rozumalski, A., Graham, H. K., & Tirosh, O. (2009). The gait profile score and movement analysis profile. Gait Posture, 30(3), 265-269.
Bjornson, K. F., Belza, B., Kartin, D., Logsdon, R., & McLaughlin, J. F. (2007). Ambulatory physical activity performance in youth with cerebral palsy and youth who are developing typically. Phys Ther, 87(3), 248-257.
Palisano, R., Rosenbaum, P., Walter, S., Russell, D., Wood, E., & Galuppi, B. (1997). Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol, 39(4), 214-223.
Palisano, R. J., Rosenbaum, P., Bartlett, D., & Livingston, M. H. (2008). Content validity of the expanded and revised Gross Motor Function Classification System. Dev Med Child Neurol, 50(10), 744-750.

Anteversion – a natural history

“Increased” femoral anteversion is one of the major impairments affecting walking in children with cerebral palsy. De-rotation osteotomies to correct this are a common orthopaedic procedure particularly as a component of single event multi-level surgery.  This post is the first of a series that will look at different aspects of anteversion and will focus on the published natural history data for the general population (i.e. those without CP).

There are several studies in the literature which have surveyed the natural history of femoral anteversion in the general population which together represent measurements of 1792 hips (Crane, 1959; Fabry, MacEwen, & Shands, 1973; Shands & Steele, 1958; von Lanz & Mayet, 1953).  The data from these series is plotted in the graph below. A couple of things are clear. Probably the most obvious is that is a huge range in measurements made at any given age (represented by the standard deviation). There is almost certainly a considerable measurement error but even so the conclusion should probably be that there is a wide range of femoral anteversion within the general population. Historical data from cadaveric specimens would appear to support this (Dunlap, Shands, Hollister, Gaul, & Streit, 1953).

Anteversion

The other consistent finding is that anteversion is high at birth and reduces with age. The data appears to suggest the mean value at birth is about 40° and has reduced to about 15° at age 16. The graph doesn’t appear to have flattened out completely by this time and other studies have suggested that the mean value amongst the general adult population may be less than 10° (Dunlap et al., 1953).

It should be noted that, at the age when children are generally being assessed for femoral derotations (8-10 years old), the average femoral anteversion is over 20° within the general population and a significant number of children (without CP) have anteversion in excess of 30° (remember that by definition 15% of the population have anteversion greater than the mean plus one standard deviation plotted here). Many kids with CP have measured anteversion in this range and for them the clinical question should perhaps not be whether they have high levels of anteversion or not but what it is that this causes them to walk with an intoed gait when many kids without CP have similar levels of anteversion but manage to walk with “normal” mild external foot progression?

It is perhaps worth pointing out that the measurements reported in these series used quite different techniques from the modern clinical measures of anteversion. The general trends are almost certainly valid but the actual values may differ when different measurement techniques are used.

Crane, L. (1959). Femoral torsion and its relation to toeing-in and toeing-out. J Bone Joint Surg Am, 41-A(3), 421-428.

Dunlap, K., Shands, A. R., Jr., Hollister, L. C., Jr., Gaul, J. S., Jr., & Streit, H. A. (1953). A new method for determination of torsion of the femur. J Bone Joint Surg Am, 35-A(2), 289-311.

Fabry, G., MacEwen, G. D., & Shands, A. R., Jr. (1973). Torsion of the femur. A follow-up study in normal and abnormal conditions. Journal of Bone and Joint Surgery, 55(8), 1726-1738.

Shands, A. R., Jr., & Steele, M. K. (1958). Torsion of the femur; a follow-up report on the use of the Dunlap method for its determination. J Bone Joint Surg Am, 40-A(4), 803-816.

von Lanz, T., & Mayet, A. (1953). Die gelenkorper des menschlichen hufge- lenkes in der progredienten phase inherer umweigigen ausformung. Zeitschrift Anatomie, 117, 317-345.