Botulinum toxin injection
When is this procedure indicated?
AUTHORIZED INDICATIONS (Not all botulinum toxin specialties possess all of the indications below):
- blepharospasm, hemifacial spasm, and associated focal dystonias;
- cervical dystonia;
- focal spasticity of the upper and lower extremities in adult stroke patients;
- focal spasticity associated with dynamic equinus foot deformity due to spasticity in ambulatory pediatric patients with cerebral palsy, two years of age or older;
- persistent and severe primary hyperhidrosis of the axillae;
- chronic migraine headaches;
- urinary incontinence due to overactive bladder or neurogenic detrusor muscle overactivity.
INDICATIONS NOT AUTHORIZED due to incomplete data regarding the safety and efficacy of the drug, but for which literature data support its use:
- spasticity, limited to forms not included in the approved indications;
- persistent and severe primary focal hyperhidrosis (palmar or facial) that interferes with normal daily activities or social relationships and is resistant to topical treatment, limited to forms not included in the approved indications;
- focal and segmental dystonias, limited to forms not included in the licensed indications (e.g., upper extremity kinesigenic dystonias, such as scribe's and musician's cramp);
- sialorrhea and other salivary gland disorders;
- post-paralytic facial synkinesias;
- tremor, tics, myoclonus, and other hyperkinetic/dyskinetic movement disorders (laryngeal dystonia).
With the AIFA determinations of July 17, 2014 and September 25, 2014, for some of the aforementioned indications (spasticity, primary focal hyperhidrosis, focal and segmental dystonias) botulinum toxin type A can be dispensed at the expense of the National Health System (NHS) pursuant to Law No. 648 of December 23, 1996, as well as to the authorized indications.
How is it performed?
The drug is administered by injection, through intramuscular, subcutaneous or intraglandular injections depending on the pathology treated.
The doctor in charge of the treatment decides the number of injections, location, dose, and frequency of treatment with botulinum toxin injections on a case-by-case basis. The therapeutic effect is established after a variable latency (usually 3-4 days) and can vary depending on the pathology, the volume of the injected muscles, as well as the dose used. In general, a peak of the pharmacological effect is normally observed after about 2-3 weeks, with a subsequent phase of stabilization and subsequent return to basal conditions in a little more than three months. The treatment with botulinum toxin is purely symptomatic and therefore will need to be repeated according to the evolution of the clinical picture and therapeutic response, however, before two months after the previous treatment: in fact, a reduction in the therapeutic effect was observed, probably mediated by antibodies blocking the molecule, for too frequent infiltrations.
The infiltration technique is relatively simple in most cases. Not infrequently, when the targets are poorly accessible, or the maximum selectivity of infiltration is required, to limit the spread of the drug and the consequent side effects, it is appropriate to perform the treatment with ultrasound guidance (sialorrhea, spasticity, cervical dystonia) or electromyography (scribe's cramp, laryngeal dystonia).
At the end of the procedure, a bladder catheter is placed and removed a few hours after the procedure.Discharge of pinkish or haematic urine is normal in the first days after the maneuver. Generally, the drug's function is evident from 7-10 days after inoculation and is maintained for a period of about 6 months. The transient paralysis that is determined by the toxin at the usual dose of 100- 200 IU results in the disappearance of incontinence and reduction of urination frequency.
The results are excellent, both clinically and subjectively, although the therapy is not completely free of complications. In some cases, extemporaneous catheterization is necessary to empty the bladder. Another possible complication is infection of the urinary tract that; however, it does not represent a serious event and is treated with normal ad hoc antibiotic therapy.
The only real complication described in literature is a transient asthenia, detected however in rare cases and in tetraplegic subjects. No true long-term complications are described in the literature.
The use of botulinum toxin is contraindicated in cases of:
- known hypersensitivity to the toxin itself or to any of its excipients;
- presence of infection at the site of administration;
- individuals with neuro-muscular junction disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome).
Use of the drug is not recommended in:
- subjects with a history of dysphagia or breathing difficulties;
- subjects with a diagnosis of neuromuscular disease;
It is required particularly in case of:
- concomitant administration of aminoglycosides or spectinomycin or agents capable of interfering with neuromuscular transmission (e.g., curare-like compounds);
- angle-closure glaucoma (or patient at risk of developing this type of glaucoma).
Reports of allergy to botulinum toxin or its excipients are extremely rare. Pharmaceutical preparations of botulinum toxin also contain human albumin. As with other blood products, the risk of transmission of infectious agents cannot be excluded with absolute certainty; however, at present there are no reports of viral transmission related to botulinum toxin treatment.
In rare cases when transient vision problems occur, the patient should not drive motor vehicles or operate machinery. Very rare cases of glaucoma have been reported.
After injection of high dosages of botulinum toxin, systemic side effects related to the spread of the toxin away from the injection site have been reported very rarely. Such effects include:
- fever and flu-like symptoms;
- weakness and general malaise;
- dryness of the mouth;
- difficulty in swallowing food or liquids, resulting in risk of aspiration into the airway;
- irregular heartbeat; heart attacks;
- seizures or convulsions, reported especially after treatment of persistent muscle spasms in the legs of children with cerebral palsy.
Side effects related to the mechanical act of infiltration rather than the pharmacological effects of the toxin include:
- pain or burning at the injection site even hours after injection;
- dizziness, blurred vision, hypotension up to syncope;
- hematoma at the site of inoculation (which does not affect the effectiveness of the treatment).
Other side effects depend on the muscle districts treated; they usually occur within the first few days of treatment and persist for a few days to two to three weeks. These effects are listed below:
1. Injections into the muscles of the eyelid and face can cause:
Common side effects:
- small bleeding under the skin, drooping of an eyelid, difficulty in closing one or both eyes completely, excessive tearing, conjunctival irritation, dry eyes, and sensitivity to light.
Less common side effects:
- blurred or double vision, inflammation of the cornea, weakness of the muscles of the face with changes in facial expression, inward or outward bending of the eyelid rim, swelling of a part of the face or eyelids.
Rare side effects:
- eye pressure elevation, corneal ulceration
2. Injections into the neck muscles can cause:
Common side effects:
- difficulty swallowing (dysphagia).
Uncommon side effects:
- sense of heavy head or weak neck, dizziness, headache, stiffness or soreness of muscles, dry mouth, change in tone of voice
3. Injections into the intrinsic laryngeal musculature:
- laryngospasm upon infiltration (rare), aphonia (frequent), dysphagia.
4. Injections into the muscles of the limbs can cause:
Common side effects:
- Weakness of the treated limb, transient pain or cramping of the treated limb, urinary incontinence (inability to control bladder emptying), diarrhea or constipation, loss of appetite, walking problems are also possible in children (with an incidence of 1-5%).
5. Subcutaneous injections at sites of excessive sweating may cause:
- increased sweating at sites other than the treated site, itching, mild and transient weakness of the hands.
6. Injections into the salivary glands can most commonly cause:
- Dysphagia or worsening of dysphagia if already present, weakness of the chewing muscles, dryness of the mouth.
Rare side effects:
- local infection of the salivary glands with redness, swelling, pain and sometimes fever, hematomas, salivary duct stones, partial lesions of the facial nerve branches.
7. Injections of the vesico-urethral system can cause:
- injection of the detrusor muscle may result in ineffective and incomplete emptying of the bladder;
- injection of the sphincter muscle may result in urinary incontinence.