Botulinum Toxin is a neurotoxin produced by Clostridium Botuli, responsible of Botulism. It’s Alan Scott, a Californian ophthalmologist who had the first the genius idea to use it for the treatment of strabismus (cross eyes) in infant, as an alternative to surgery. He saw very quickly the potential of the Botulinum toxin for the treatment of movement disorders in the ophthalmology sphere such as hemifacial spasm and blepharospasm.

In Europe it’s also started with the ophthalmologists, in particular John Lee and John Elston in London, spreading quickly to the neurological community of movement disorders specialists, with David Marsden at King’s college hospital and his large research fellow group, who each took back the treatment to their own country (France, Germany, Italy, Spain). I had the privilege to be the pioneer of this technique in France, when returning from London in 1986.

The therapeutic adventure of the Botulinum toxin had started and since has never stopped.  The last 30 years has seen the Botulinum toxin becoming an invaluable therapeutic tool for every medical and surgical specialty.

2-Medical specialties using Botulinum toxin

The Botulinum toxin has been used in most of medical specialties in addition to ophthalmology and neurology, such as ENT (voice disorders, swallowing difficulties), maxillo-facial (jaw spasms, drooling), rehabilitation (spasticity in children with cerebral palsy and in adults following stroke and MS), urology (hyperactive bladder) and dermatology (wounds, scar tissue).

3- Therapeutic contribution of Botulinum toxin to neurology

Movement disorder: dystonia and spasticity

Botulinum toxin has been a therapeutic revolution in the treatment of muscle spasms such as dystonia and spasticity. Over these last 30 years, the injection of Botulinum toxin has showed its efficacy and its long term safety.

Focal dystonia, starting in adulthood, is the cause of functional disability as the dystonic muscle spasms interfere with a function such as opening eye (blepharospasm), moving head (cervical dystonia), writing (writer’s cramp) , chewing (oromandibular dystonia) , speaking and breathing ( laryngeal dystonia). The most efficient treatment is the injection of Botulinum toxin into the dystonic muscles.

The treatment of spasticity in children with cerebral palsy has allowed these children to regain a function such as walking and is part of a more holistic approach with physiotherapy, casting and surgery. The treatment of spasticity in adults following stroke or Multiple sclerosis has also change the functional prognosis of these conditions.

Tremor

Botulinum toxin is the treatment of choice in head tremor (both dystonic and essential tremor), in voice tremor, in Holme’s tremor following brain injury for instance, in some task specific tremor and in palatal tremor

– Pain

Botulinum toxin injections (Botox, Allergan) have the licence in the treatment of chronic migraines and are part of NICE guidelines for the treatment of migraines.

Also recent publications report the effect on peripheral neuropathic pain  (diabetic neuropathy, post-herpetic neuralgia).

– Hyperhidrosis.

Botulinum toxin is the most efficient treatment of the different localisations of excessive sweating such as axillae (armpit), palmar and cranio-facial ( scalp and face) hyperhydrosis. The botulinum toxin blocks the secretion of the sweat glands. The effect is usually more prolonged than for muscles spasms.

Drooling

Children with cerebral palsy and adults with Parkinson’s disease are among patients who benefit from injection into the salivary glands (parotid and submandibular glands) to control drooling, avoiding choking on saliva and great social embarrassment.

4 – The Botulinum toxin, a clinical research tool

Apraxia of eyelid opening is a non paralytic, motor difficulty in initiating the act of lid elevation, so the patient can’t open the eyes. It affects patients with blepharospasm, or with parkinsonism and sometimes occurs in isolation. Botulinum toxin has allowed clinicians to elucidate the underlying mechanism of so called Apraxia of eyelid opening, showing that injection into the pretarsal part of the eyelids, along the eyelashes facilitates the opening of the eyes of the patients with this condition.

Breathing laryngeal dystonia is responsible of a stridor, due to vocal cords in paramedian position. The disappearance of the stridor following the injection of Botulinum toxin into the vocal cords muscles (adductor muscles), in dystonic patients showed that the paralysis of the abductor muscle of the vocal cords was not the only cause of stridor, but that dystonic spasms in adduction of the vocal cords could be involved in some clinical presentation.

Expression of emotions

Botulinum toxin has been used to explore the physiological mechanisms of emotions, and in particular to test the facial feedback hypothesis. The control of the expression of facial emotions could influence in parallel subjective feelings or emotional experience. Women following injections of the frowning muscle (corrugator muscle) with Botulinum toxin are less able to mimic anger or sadness expression and show less activation in limbic region (amygdala) compared to women injected with placebo.

Botulinum toxin injections into the corrugator muscles have also been tested in the treatment of depression, with success supporting the concept, that the facial musculature not only expresses, but also regulates mood states.

5-Widening the Use of Botulinum toxin: The Next Frontier

New development are taken place in rheumatology (musculoskeletal pain), gynaecology (pain) and in psychiatry (depression), oncology and even the cardiology, for which you will think it will never occur, as the heart muscle should be kept away from any weakening muscle agent, with recent study of its role in post surgical dysrythmia.

Botulinum toxin treatment has been a major therapeutic advance in neurology and other medical specialties. The list of the indications is constantly widening and its application goes much beyond its cosmetic use.