How doctors think--and treat with botulinum toxin.

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How doctors think – and treat with botulinum toxin
A Sebastian Schroeder1, Inga Koerte2, Steffen Berweck3,
Birgit Ertl-Wagner2, Florian Heinen1
1 Department of Paediatric Neurology and Developmental Medicine, Dr von Hauner's
Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.
2 Institute of Clinical Radiology, Ludwig-Maximilians-University of Munich, Munich,
Germany. 3 Specialist Centre for Paediatric Neurology, Epilepsy Centre for Children
and Adolescents, Vogtareuth, Germany.
Correspondence to: sebastian.schroeder@med.uni-muenchen.de
doi: 10.1111/j.1469-8749.2010.03692.x
SIR–A recent bestseller in popular medicine is How Doctors
Think by Jerome Groopman.1This book narrates true stories
that illustrate how some doctors went spectacularly wrong
because they were trapped in their established ways of think-
ing unable to adjust to newly emerging evidence. Even in the
face of new compelling data doctors tend to stay with their old
concepts.
Here we add a note about botulinum toxin type A
(BoNT-A), a substance used worldwide in applications
ranging from (child) neurology to aesthetics, contributing to
significantly improved medical care in one field and generating
big business in the other.
BoNT-A injections are performed thousands of times every
day worldwide. Based on the evidence accumulated in over
10 000 publications (PubMed search under ‘botulinum toxin’)
there is general consensus that the clinical effect of BoNT-A
lasts for about 3–6 months. Therefore, in keeping with clinical
observations and seemingly supported by data from animal
experiments,2BoNT-A is usually reinjected at 3- to 6-month
intervals. Recent data on the duration of neurogenic atrophy
after injection into healthy human muscle have had little
impact on clinical practice so far3,4and data on spastic muscle
are missing.
Using three Tesla magnetic resonance imaging (MRI) with
water sensitive T2-weighted short tau inversion recovery
sequences we report a 1-year follow-up examination in a
male with cerebral palsy after a single injection of BoNT-A
into the lower leg according to published recommendations.5
The treated muscle shows the same high signal intensity
pattern (Fig. 1) as previously reported for healthy volun-
teers,4indicating that focal neurogenic atrophy at the site of
injection is still present 6 months (and to some extent 1 year)
after BoNT-A injection.
Since its introduction in the 1980s, and encouraged by posi-
tive clinical effects, BoNT-A has been used ahead of a com-
prehensive fundamental knowledge about its biological effects
in humans. The data on spastic muscle presented here are con-
sistent with earlier observations in healthy muscle4indicating
that focal neurogenic atrophy following BoNT-A persists
longer than expected. The discrepancy between the observed
‘focal long-term structural alterations’ and the clinically
reported ‘short-term functional efficacy’ remains unclear. This
should induce further investigations and provoke reconsidera-
tion of the established regimes of BoNT-A treatment.
6wks
6mo
12mo
*
HSIP
a
b
*
*
Figure 1: T2 short tau inversion recovery (STIR-) MR sequence, time course of BoNT-A in the lower leg. Male (9y) with unilateral spastic CP of the right body
side (Gross Motor Function Classification System (GMFCS) level I). Injection of BoNT type A (preparation Botox?) into two sites of the right soleus at the mid-
dle of the lower leg: medial site 50 Units, lateral site 50 Units. The high signal intensity pattern (HSIP) in short tau inversion recovery (STIR) MR sequence of
the lateral injection site of soleus muscle can be seen in the encircled area. (*) indicates the HSIP in the medial injection site. (a) Coronal view of the lower
legs 6 months after injection. (b) Axial view of the same patient over course of 12 months.
ª The Authors. Journal compilation ª Mac Keith Press 2010
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DEVELOPMENTAL MEDICINE & CHILD NEUROLOGYLETTER TO THE EDITOR

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Visualization of BoNT-A injection using ultrasound was a
first step to improve intervention.6Follow-up visualization of
BoNT-A-induced muscle alterations using MRI could well be
the next step.
REFERENCES
1. Groopman J. How Doctors Think. Boston, MA: Houghton
Mifflin, 2007.
2. de Paiva A, Meunier FA, Molgo ´ J, Aoki KR, Dolly JO. Func-
tional repair of motor endplates after botulinum neurotoxin
type A poisoning: biphasic switch of synaptic activity
between nerve sprouts and their parent terminals. Proc Natl
Acad Sci USA 1999; 96: 3200–5.
3. Wohlfarth K, Mu ¨ller C, Sassin I, Comes G, Grafe S. Neuro-
physiological double-blind trial of a botulinum neurotoxin
type A free of complexing proteins. Clin Neuropharmacol
2007; 30: 86–94.
4. Schroeder AS, Ertl-Wagner B, Britsch S, et al. Muscle biopsy
substantiates long-term MRI alterations one year after a sin-
gle dose of botulinum toxin injected into the lateral gastroc-
nemius muscle of healthy volunteers. Mov Disord 2009; 24:
1494–503.
5. Heinen F, Desloovere K, Schroeder AS, et al. The updated
European Consensus 2009 on the use of botulinum toxin for
children with cerebral palsy. Eur J Paediatr Neurol 2010; 14:
45–66.
6. Berweck S, Schroeder AS, Fietzek UM, Heinen F. Sonogra-
phy-guided injection of botulinum toxin in children with
cerebral palsy. Lancet 2004; 363: 249–50.
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Developmental Medicine & Child Neurology 2010