Update in Botulinum Toxin Use: Taking Advantage of Your Resources

By: Darryl L. Kaelin, MD

In managing patients with spasticity, especially when injecting botulinum toxin, there is one motto that holds true. It’s that the more one thinks he knows the more there really is to learn. Whether it is patient criteria, medication use or muscle selection for injection, nothing is as straight forward as it seems.

It is the goal of this article to review the factors that form the basis for selection of botulinum toxin therapy in adult patients. The features of botulinum type A and type B will be compared. Finally, techniques and resources available to the clinician in determining when botulinum might be effective and in which muscles will be introduced.

When considering spasticity management the physician needs to take into account the patient’s physical presentation as well as the goals that they and their care providers have. Positive symptoms of upper motor syndrome include spasticity, heightened reflexes, clonus, and synergy patterns of movement.

Negative symptoms include weakness and loss of selective muscle control and dexterity. Rheologic changes such as stiffness, contracture, and atrophy play a role into which intervention might best meet the goals of treatment. The clinical distribution of spasticity also dictates the type of intervention that will be most beneficial.

Standardized definitions have not been made, but for the benefit of this article we will divide spasticity patterns into isolated, focal, segmental, multisegmental and generalized. Isolated spasticity affects one muscle, while focal spasticity affects one muscle group such as elbow flexors.

Segmental spasticity involves a functional muscle group such as flexors of the fingers, wrist, elbow and shoulder. Multisegmental spasticity involves two segments as can be seen in hemiparesis. Generalized spasticity affects more than two limbs and possibly the trunk.

As a rule of thumb the fewer muscle groups affected the more amenable they are to botulinum toxin therapy. While multisegmental or generalized spasticity may respond to botulinum it is usually best treated with medications, intrathecal baclofen, or surgery.

Patient and caregiver goals are very important to take into consideration. The physician needs to ask in what way the spasticity is affecting the patient. Then it should be decided if the goals are to increase function, reduce pain, or to improve hygiene or quality of life. It is only after these preliminary steps have been taken that the success of treatment can be evaluated.

Once one has decided that botulinum toxin (BTX) is indicated there are currently two choices available in the United States, BTX-A (Botox) and BTX-B (Myobloc). Additionally, botulinum type A is produced internationally as Dysport and as NT 201 in Germany. Botulinum type B is produced internationally as NeuroBloc.

All botulinum toxins cleave one or more vesicle fusion proteins, thus blocking the release of acetylcholine from the axon terminals of motor neurons, preganglionic sympathetic and parasympathetic neurons, and postganglionic parasympathetic nerves by a multi-step mechanism that varies slightly, but significantly, for each serotype.

BTX-A affects the SNAP-25 protein, whereas BTX-B affects the vesicle-associated membrane protein, also known as synaptobrevin. In spasticity, the effect of BTX-A becomes evident within 12 hours to 7 days, and the duration of effect lasts 3-4 months.

The comparative onset and duration of BTX-B requires further study, although, in practical use, the rate of BTX-B has been shown to be faster than BTX-A in cosmetic dermatology settings.

Using EMG studies to record muscle activity, the data suggests that BTX-B exhibited significantly less spread to adjacent and distant muscles not injected compared with BTX-A. This in contrast to clinical studies that suggest BTX-B more commonly causes the systemic anticholinergic side effect of dry mouth.

The main uses of BTX-A and BTX-B in spasticity exploit blockade of the neuromuscular junction; however, there is emerging evidence that botulinum toxins may have analgesic effect separate from other actions, that may explain its pronounced effects on pain.

Although both BTX-A and BTX-B seem to have analgesic benefit comparison studies are lacking.

Dosing remains controversial, however, adult dosing guidelines have recently been developed by a consensus panel of clinicians: (http://www.mdvu.org/library/dosingtables/btxb_adg.html. andhttp://www.mdvu.org/library/dosingtables/btxa_adg.html).

Originally, Flynn recommended a 50:1 ratio of BTX-B to BTX-A in the dermatologic population based on studies in patients with cervical dystonia.

The recently published guidelines support a slightly lower ratio of 30-40:1 especially in first time patients or in those being converted from BTX-A to BTX-B. BTX-A and BTX-B are also supplied differently.

BTX-A is packaged in single-use vials containing 100 units of vacuum dried botulinum, which must be reconstituted prior to use.

BTX-B is supplied in ready-to-use solution in three multiple use vials of 2500 U, 5000 U, and 10,000 U at a dosage concentration of 5000 Units/ml. It is important to remember that each BTX-B vial is overfilled and actually contains 4100 U, 6800 U and 12,650 U respectively.

Currently BTX-A is FDA approved for the treatment of strabismus, blepharospasm, hemifacial spasm, cervical dystonia, and hyperhidrosis, as well as, cosmetically for severe glabellar lines. BTX-B has FDA approval for cervical dystonia.

Once a toxin has been selected for treatment determining where to inject is very important. Patient evaluation is the first and most critical step. One must test the joint range of motion both passively and actively to measure the severity of spasticity using a standardized scale, the degree of soft tissue restriction or contracture, and how much underlying functional strength remains.

Peripheral nerve blocks or motor point blocks with lidocaine can help the clinician decipher if restricted range of motion is from muscle over-activity or fixed contracture. Restricted active movement can also be the result of co-contraction of antagonistic muscles.

Patients should be examined both in static position as well as dynamically.

Optimal criteria for functional gain using botulinum toxin therapy include focal or segmental spasticity, retention of selective motor control, and minimal fixed contracture. Patients who fall outside this definition may still meet goals in other areas.

A good knowledge of both anatomy and kinesiology are necessary to determine which muscles may best respond to BTX treatment.

There are several muscle localization techniques that may be available to the physician in the clinical setting. These include palpation, multi-channel EMG, dynamic gait analysis, electrical stimulation, and ultrasound.

The traditional method of palpation can be effective, nonetheless, in an attempt to increase accuracy and reduce medication load this technique is only recommended for large easily palpable muscles such as the biceps.

Most physicians in practice do not have readily available gait labs making this technique less convenient. This may be a method of choice in patients with complicated mobility problems such as adults with cerebral palsy.

The cost of multi-channel surface or wire electrode EMG equipment is coming down yearly and what was once available only in research labs or large spasticity clinics is now cost-effective for the physician regularly managing Upper Motor Syndromes.

By measuring motor unit recruitment of several muscles firing simultaneously during as specific movement, the clinician can determine which muscles are weak, which are spastic and which co-contract.

This technique appears to give the best diagnostic evaluation as to which muscles are involved in abnormal function and how treatment can be delivered to the most beneficial location.

An excellent 16 channel EMG machine is the TeleMyo 2400 manufactured by Noraxon Inc. In the event that a physician does not have access to multi- channel capabilities, a single or two channel EMG machine can provide the “poor man’s” technique.

Simply place the needle electrode into the agonist muscle and fire both the agonist and then its antagonist. Normally, one is looking for the agonist to fire “in phase” and to remain silent “out of phase”. If a muscle co-contracts out of phase then it will resist the desired movement.

Additionally, passive stretch of a muscle will cause it to fire spontaneously if it is spastic. This is what I term tonic spasticity which is frequently observed in Upper Motor Syndromes like stroke and brain injury.

This is compared to phasic spasticity where motor units are actively firing with muscles in static position. This is commonly seen in cervical dystonia. As an example, a physician using a long electrode wire can determine if the Tibialis Anterior or Tibialis Posterior is most causing the inversion seen with equinovarus changes during stance or short distance ambulation.

These techniques are especially helpful to surgical colleagues trying to decide which tendon to lengthen and which to transfer. For muscle specificity, electrical stimulation is very effective in isolating muscles and even the muscle fascicles involved in abnormal tone. An EMG injection needle can serve both as your stimulator and as the mechanism of drug delivery.

Peripheral stimulators cost only a few hundred dollars and can be particularly helpful in finding small muscles of the hand and forearm. They serve a dual purpose in peripheral nerve and motor point blockade.

An example of a portable peripheral nerve stimulator is the EZstim II, model ES400, manufactured by Life-Tech, Inc. (www.life-tech.com). Lastly, ultrasound has entered the scene as a newer technology for identifying proper muscle injection localization.

Its advantages are in that it gives a more virtual picture of the actual muscle and can be used for other diagnostic purposes. Its disadvantages are in its cost and significant training time.

As physicians managing individuals with acquired brain injury and spasticity, we are entering a new era. We can no longer be satisfied with injecting BTX into any tight muscle group and hoping it finds its way to the right place.

We must keep up with the rapid pace of newly acquired knowledge and technology in order to provide our patients with the best health-care.

With compassion, effort, and the right equipment even individual private practitioners can manage spasticity like they ran a large university-based clinic.

For more information on comprehensive management of spasticity please visit www.wemove.org and login to the MD virtual university.

 

Darryl L. Kaelin, M.D.
Medical Director of Brain Injury Services
Shepherd Center
Assistant Clinical Professor
Dept. of PM&R, Emory University
Atlanta,GA
(o)404-350-7353
(f) 404-350-7381

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