This presentation reviewed the story of the use of Botulinum Toxin in neurology in France in 1986 by Dr Marie-Helene Marion,

1. “Les Amis du
Clostridium”
Dr Marie-Helene Marion
Consultant neurologist
Chair of the BNN
Alan Scott, Toxins
meeting, 2015

2. How it all started in Europe?
• J.Elston:
– Back from San Francisco, started injecting at
Moorfields Hospital and at Denmark hill
(CDM)
– published on BSP-1985 with Prof Ross
Russell about patients from Moorfields, CD
Marsden and Ian Mc Donald
– HFS- 1986
• 2 toxins:
– Oculinum by Smith-Kettlewell Eye Research
Foundation ( Alan Scott- SF)
– Toxin A by Porton Down products ( Vaccine
research and Production laboratory)
• MHM at Denmark Hill Sept 1983- July 1985
in CD Marsden department.
Mr John Elston
May 1984, opening ceremony KCH

3. Which Toxin and which dosage
in 1985?
• “We initially used botulinum toxin A
supplied by Professor Schantz of the
University of Wisconsin;
• We subsequently used botulinum toxin A
supplied by Professor Melling of the Vaccine
Research and Production Laboratory, Porton
Down, at the same dose.
• Although the median lethal doses of these
two preparations had been found to be the
same in mice, we later found that the
botulinum toxin A from Porton Down was
more neurotoxic in man and so we reduced
the dose, a total of 1.50 ng( 60 units) in 2
ml saline being injected around each eye.”
1985, Elston
Side effects
-Ptosis
-Diplopia due to
diffusion to inferior
oblique or to superior
rectus
- Persistent Bells
phenomenon

4. Kremlin-Bicetre Hospital , Paris 1986
• Chef de clinique in the
department of Prof Jean
Lapresle, after ethical committee
approval ( GREBB).
• First patients were admitted for
the injection!
• Toxine A: 1 vial 2000 units in 10
ml saline= 50 ng HA-complex.
• Treatment on HFS with
Botulinum toxin – presentation at
SFN on July 1987
Prof Jean Lapresle
1 vial of 2000 units of botulinum toxin

5. How did I get the Toxin
in France?
• Initially importation on patient‘s name basis of
the Botulinum toxin from CAMR, Porton down (
Peter Hambleton) in May 1986
– If you have any problem, contact John Elston at
Queen Square!
• Then importation for every batch from Porton
Down by Chimos company, Paris.
– after authorisation of importation by the chief
pharmacist from the French Health minister for every
batch 1988-1993
– Criterias: Indications, department, injection protocol
(Moorfields), training, safety policy.
– 267-290 French Francs/vial (Dec 90) May 1991
• 1991-Porton down products, UK ( P. Hambleton
laboratory, Steven Hill, therapeutic manager,
David Cox, business manager France)
– Dysport 500 units, Porton products, 12.5 ng, price x 4
Authorisation from chief pharmacist,
1988
Delivery notice for each batch of Toxin
from Chimos, 1988

6. • Oculinum 100 units (Allergan)
• Dysport 500 units ( Porton down)
Licence in France in 1993
Meeting in Paris, 1991
with UK speakers
Meeting in Paris, 1993
with French speakers
2nd ENS Brighton, 1990

7. The spread of the technique in France
• 1986: 2 centres
• 1990: 10 centres
• 1993: 43 centres
• 2016:+ 150 centres
From Alan Scott presentation, Toxins 2015

8. The multidisciplinary approach
• 1989, 1990: ENT Kremlin- Bicetre with Christine Le
Pajolec, ENT surgeon
– 1st patient , 40 years old, 20 years with Palatal
myoclonus and objective tinnitus, frequency
80/minute
– 40 units Dysport divided in 2 sites into levator veli
palatini
– Le Pajolec, Marion, Ann Oto-laryng (Paris), 1990
• 1989: ENT Fondation Rothschild :
– Laryngeal dystonia with Patrick Klap, ENT surgeon,
– Laryngeal EMG with Alain Perrin, neurophysiologist.
– Achalasia with Herve Gompell, gastro-enterologist
- 1995: Plastic surgeon: Expression lines with
Benjamin Asher
- 1995: Paediatric rehabilitation consultant: Spastic
children with Alain Lespargot
Palatal myoclonus
Palatal Muscles

9. Spasmodic dysphonia
UCL, July 1991
F. Rotschild, Nov 1993
Blitzer A, Brin MF et al, Localised injection of
Botulinum toxin for the treatment of focal
laryngeal dystonia ( spastic dysphonia)
Laryngoscope , 1988
Klap P, Marion MH et al, Treatment
of SD with Botulinum Toxin
Ann. Oto-Laryng ( Paris) 1991
Ludlow CL et al, Effects of Botulinum
Toxin injections on speech in adductor
spasmodic dysphonia Neurology 1988
Marsden CD, Sheehy MP: Spastic
dysphonia, Meige disease and torsion
dystonia. Neurology, 1982

10. Andrew Blitzer’s visit in July 1991
“One of the most memorable time …
I enjoyed seeing your patients; they were certainly a challenging lot….”

11. Stridor and focal laryngeal dystonia, 1992
Adductor laryngeal breathing dystonia
• Gerhardt’s syndrome (described in 1863).
– Attacks of laryngeal inspiratory dyspnea with normal voice with permanent adduction of
the vocal cords in paramedian position
– Due to a paralysis of the abductor muscles (MSA, MND, syphillis, herpes infection,
isolated)
• Stridor and focal laryngeal dystonia (Marion et al, Lancet 1992),
– 6 patients among 3 isolated and 3 with multifocal dystonia (Meige syndrome
and cervical dystonia)
– with immobile VC in parmediane position on fiberoptic laryngoscopy
– Inspiratory stridor during the day, which disappeared during sleep and
Increase by exercise, eating, drinking.
– On EMG, bursts of activity of 2 sec in TA
– Dystonic spasm of the adductor muscles on respiration, with normal voice
– Abolished by injection of Botulinum toxin

12. Apraxia of eyelid opening
• Apraxia of lid opening (Goldstein-Cogan, 1965)
– Non-paralytic motor abnormality characterised by the
patient’s difficulty in initiating the act of lid elevation
• Inhibition of the levator palpebrae (Lepore-Duvoisin,
1985)
• Akinesia of eyelid opening (Fahn, 1988)
• A new variant of blepharospasm (Elston, 1992)
– 10 patients, 5 isolated, 3 PD and 2 PSP
– Main group of non responders
– “Pretarsal blepharospasm”
– But technical difficulties to inject in pretarsal

13. Krack and Marion Mov Disorders,1994
Apraxia of eyelid opening:
a focal palpebral dystonia
Prof Paul Krack
•32 patients: 20 BSP, 3 pure AEO, 7 PSP, 2
PD
•Hold their head backwards
•Sensory trick touching temporal regions
•Marked frontalis contractions
•Opening eyes passively was effortful
•Able to have normal opening eyes action
•Good response to pretarsal injections in
83% patients
Pretarsal injections
Part of a clinical spectrum
of dystonia of the
orbicularis oculi

14. Conclusion
• A therapeutic revolution
• A research tool (Stridor,
Apraxia of eyelid opening)
• A personal adventure with
friendships all along through
colleagues from other
disciplines and trainees.
• A unique relation with patients

15. Les Amis du Clostridium !