Treatment Approach

Once it has been determined that a patient's symptoms of focal muscle spasm or focal neuropathic pain are a complication of RFS, initial management should start conservatively and progress to more interventional therapies, such as BTX injection, based on the patient's response to therapy. A few common clinical scenarios will be detailed. All dosing is for BTX type A (BTX-A; Botox®, Allergan, Inc., Irvine, CA), which is used preferentially in cancer patients because of its efficacy, duration of action, predictable spread within tissues, and minimal systemic absorption.

Radiation-induced trigeminal neuralgia is a common complication of radiation to the head and neck for nasopharyngioma and other neoplasms. Extensive surgical resections are often used with radiation and may significantly contribute to damage of one or more branches of the trigeminal nerve. The symptoms of trigeminal neuralgia may be in any trigeminal nerve distribution, with V2 and V3 being the most common. The anterior neck is also commonly affected because of damage to the cervical plexus. Symptoms are generally ipsilateral to the side of the tumor but can be bilateral.

Initial treatment of radiation-induced trigeminal neuralgia is similar to that for idiopathic or traumatic etiologies of trigeminal neuralgia. Conservative therapy such as skin desensiti-zation and transcutaneous electrical nerve stimulation may be of limited benefit. "Nerve stabilizing" medications can be useful. Pregabalin is generally our preferred initial medication, particularly in the cancer population, because of its efficacy, rapid onset of action, lack of drug-drug interactions, and favorable side effect profile (44). Doses higher than 600 mg per day may be used if there is incremental efficacy without a significant increase in adverse events, such as somnolence or peripheral edema. Other nerve-stabilizing medications, such as oxcarbazepine, carbamazepine, and phenytoin, can be considered as alternatives but are prone to more serious adverse events. The addition of medications with differing mechanisms of action is often beneficial but may run the risk of potentiating additive side effects (such as somnolence) and drug-drug interactions (45). Tricyclic antidepressants (amitriptyline, nortriptyline), serotonin-norepinephrine re-uptake inhibitors (duloxetine, venlafaxine), and narcotics (methadone, oxycodone) may improve efficacy when combined with drugs that have differing mechanisms of action such as pregabalin (46).

If conservative and pharmacological therapies have not resulted in adequate pain reduction in radiation-induced trigeminal neuralgia, then the addition of BTX injections should be

Trigeminal Pain Mechanisms
Fig. 6.

considered. Treatments with even partial efficacy should not be withdrawn until adequate efficacy with the BTX injections has been achieved. It may take several treatments until the location and dosing of the injections is optimized. In most patients, multimodal treatment is generally required to achieve satisfactory pain control.

Botox For Trigeminal Neuralgia Pain

Fig. 6. (Continued) Radiation-induced trigeminal neuralgia resulting from surgical and radiation treatment of a left maxillary sinus squamous cell carcinoma. Note the extensive surgical resection of the left face including eye enucleation. The patient suffers from severe trigeminal neuralgia in a partial V2, V3, and anterior cervical distribution. Two hundred units of botulinum toxin into 5 cc of normal saline produces a concentration of 5 U/0.1 cc. Injections of approximately 0.1 cc are spaced about 1.5 cm apart (illustrated by black dots) should spread to cover all affected skin.

Fig. 6. (Continued) Radiation-induced trigeminal neuralgia resulting from surgical and radiation treatment of a left maxillary sinus squamous cell carcinoma. Note the extensive surgical resection of the left face including eye enucleation. The patient suffers from severe trigeminal neuralgia in a partial V2, V3, and anterior cervical distribution. Two hundred units of botulinum toxin into 5 cc of normal saline produces a concentration of 5 U/0.1 cc. Injections of approximately 0.1 cc are spaced about 1.5 cm apart (illustrated by black dots) should spread to cover all affected skin.

BTX injections will be performed intradermally or subdermally over the areas of skin affected as determined by the patient's historical account and the physician's physical exam. BTX-A is delivered in 100 U vials that are stored frozen and must be reconstituted with normal saline. The concentration of BTX can be varied at the physician's discretion based on how much saline is used to reconstitute the toxin. In general, 2.5 cc of normal saline injected into a 100-U vial is used to produce a concentration of 5 U per 0.1 cc.

The anticipated amount of spread of BTX-A is approximately 1 cm from the site of injection (2 cm diameter) from 5 U in 0.1 cc in normal skin. Spread is probably significantly lower in patients affected by radiation fibrosis because of the abnormal accumulation of protein. Injections should be spaced about 1.5 cm apart so that the spread from each injection overlaps the next and all affected skin is covered (Fig. 6). It is not necessary to cover all radiation-damaged skin, only the skin that the patient reports is painful or physical examination determines to be dysesthetic or allodynic.

The usual starting dose of BTX needed to treat radiation-induced trigeminal neuralgia is about 100 U. More BTX should be used if the area of skin to be injected is extensive. The skin should be clean and sterilized with alcohol. Patients should be encouraged to not wear makeup to the office visit. A 30-gage needle is generally used and syringe size ranges from 1 to 10 cc based on physician preference. Smaller syringes allow for more precise volume delivery and should be used by beginning practitioners. With practice, the volume of solution injection into the patient can be accurately determined by the size of the bleb raised under the skin.

Table 1

Disorders of Focal Neuropathic Pain Associated With RFS

Disorder BTX-A dose range (units)

Intercostal neuralgia 50-300

Migraine 50-200

Occipital neuralgia 50-300

Post-mastectomy syndrome 50-300

Stump pain 100-300

Thoracic radiculopathy 50-300

Trigeminal neuralgia 50-300

RFS, radiation fibrosis syndrome; BTX-A, botulinum toxin type A.

It is common for initial BTX injections to only provide a partial benefit, generally resulting from either failure to overlap the spread from injections, too low a concentration of BTX in each aliquot delivered, or a penumbra effect. The penumbra effect occurs when the most severely affected skin is adequately treated but the surrounding, less affected areas are not. In such cases the injection procedure should be modified to include more of the surrounding skin. Closer spacing of BTX injections should be used if spread is insufficient. A more concentrated BTX solution should be considered if the injections are properly spaced and all affected skin is covered, but the patient still has inadequate efficacy.

The effect of BTX injections in radiation-induced trigeminal neuralgia should take approximately 2 to 3 days to begin and are maximal at about 10 days. EMLA cream can be used pre-procedure and ice post-procedure to alleviate discomfort. The area injected can be gently washed but makeup should not be applied for several hours to decrease the chance of it entering or irritating the skin. Normal activities can be resumed following injection without limitation.

The major potential complication of BTX injections for radiation-induced trigeminal neuralgia is infection. Weakening of the orbicularis oris or orbicularis oculi may cause or worsen drooling and ptosis respectively. Injection over the anterior neck can cause dysphagia or dysarthria. Wrinkles on the face may be reduced. This is often considered a cosmetic benefit in patients whose face has been deformed by the radiation and scaring of treatment but is not pleasing to all patients. Weakness caused by BTX injections is not permanent and should resolve spontaneously in approximately 6 weeks.

It should be noted that the techniques used for radiation-induced trigeminal neuralgia are likely widely applicable to any focal neuropathic pain disorders associated with radiation (Table 1).

Radiation-induced trismus is a complication of RFS and may co-exist with radiation-induced trigeminal neuralgia. Ectopic activity in trigeminal nerve motor fibers resulting from radiation fibrosis results in spasm and pain, particularly in the masseter. Unchecked, persistent spasms of the masseter can contribute to fixed contracture and ultimately inability to open the jaw. Patients with severe trismus and jaw contracture may have difficulty speaking and may not be able to ingest food or liquid orally.

Antispasmodic medications may offer some relief from spasms. Nerve stabilizers such as pregabalin and analgesics such as oxycodone have some efficacy in relief of pain. A trial of medications should be used initially to relieve pain and spasms. Often more than one medication with differing mechanisms of action is required. Evaluation and treatment by physical, occupational, or speech therapy is extremely important and should be ordered early in the course of disease. Therapy should emphasize maintenance of jaw excursion to prevent progression to fixed contracture. Treatment of fixed jaw contractures required progressive static or dynamic stretching using such devices as tongue depressors or the Therabite® system (41,47).

BTX injections may alleviate the spasm and pain associated with radiation-induced trismus but will not directly treat jaw contracture. The masseter is most often targeted but injection into the temporalis muscle may also be useful in some instances. Although the medial and lateral pterygoid muscles may be involved in radiation-induced trismus, their location behind the ramus of the maxilla makes their injection difficult. It should be noted that the masseter is commonly subject to resection depending on tumor type, extent, and location. The presence or absence of a masseter (palpable on the ramus of the jaw with volitional jaw clinching) may not always be obvious on physical examination because of scar and deformity. When the anatomy is uncertain, surgical records and imaging (MRI) should be reviewed before initiating BTX injections for trismus to be sure of the presence and location of critical structures. Injection can be either unilateral or bilateral depending on the patient's anatomy and symptoms.

EMG guidance is very useful to confirm needle placement within the masseter, which is often atrophic and fibrotic. Marked spontaneous activity including fibrillation potentials, positive sharp waves, myokymia, and fasciculation potentials are usually seen. A hollow monopolar needle (such as the Ambu® Neuroline Inoject) is used. Needle size varies but a 30-mm, 28-gage needle is usually sufficient to achieve adequate muscle purchase in most patients.

Because of the size of the masseter, no more than 0.5 to 1 cc of volume is typically injected. The volume injected should be divided into two to three muscle sites, preferably in and around the motor endplate zone. The concentration of BTX varies to accommodate the total number of units the clinician intends to inject. For instance, if 50 U in 0.5 cc are to be injected, then 1 cc of saline should be used to dilute a 100-U vial of BTX-A. The dose used varies from 25 total units per masseter at the conservative end to as high as 200 or more units per masseter as needed by the patient's response to past injections. The site of injection should be sterilized with alcohol. Titration of dose should occur at approximately 6-week intervals unless symptoms are so severe as to warrant rapid dose escalation on repeat injections every several days.

The technique and doses used for injection of the temporalis is similar but EMG guidance is not generally needed. A 30-gage needle should be used to inject at least four separate sites within the temporalis.

The major potential complications of injection for radiation-induced trismus include infection and bleeding. Dysphagia and dysarthria are uncommon at lower doses of BTX but become more likely as doses are increased.

Radiation-induced cervical dystonia can result not only from the treatment of head and neck cancers, but from treatment of any tumor treated with radiation that involves occiput, cervical spine, or upper thoracic spine (48). This includes metastatic disease from any cancer type, sarcomas, lymphomas such as Hodgkin's disease, thyroid cancer, and so on.

Idiopathic cervical dystonia is broadly defined as a movement disorder characterized by involuntary contractions of the head and shoulders, which may be twisted into aberrant positions including torticollis, laterocollis, retrocollis, and anterocollis (49). In radiation-induced

Table 2

Disorders of Focal Muscle Spasm Associated With RFS

Table 2

Disorders of Focal Muscle Spasm Associated With RFS

Disorder

Muscle

BTX-A dose range (units)

Trismus

Masseter

25-200

Cervical dystonia

Cervical paraspinals

25-200

Levator scapulae

25-50

Longissimus

25-100

Scalene complex

10-50

Splenius capitis

50-100

Sternocleidomastoid

10-50

Trapezius

25-100

RFS, radiation fibrosis syndrome; BTX-A, botulinum toxin type A.

RFS, radiation fibrosis syndrome; BTX-A, botulinum toxin type A.

cervical dystonia, radiation fibrosis likely contributes to ectopic activity in the distribution of the spinal accessory nerve and cervical nerve roots, which may be asymmetric and cause aberrant positioning of the head and neck. More often, symptoms are at least partially bilateral. As radiation fibrosis progresses, posturing of the head and neck becomes less pronounced and fixed contractures develop. Most patients complain of neck tightness that progresses slowly and insidiously and is almost always accompanied by pain. Inability to position the head because of progressive fibrosis can affect swallowing, phonation, and activities of daily living, such as driving and work-related tasks.

As in radiation-induced trismus, the natural history of radiation-induced cervical dystonia is one of progression. Aggressive physical therapy with emphasis on a life-long home exercise program designed to maintain head and neck range of motion is critical. It is generally easier to prevent a contracture than to treat one. Medications may be useful in treating the symptoms of radiation-induced cervical dystonia but cannot substitute for range-of-motion exercises. Medications of possible benefit are similar to those discussed in the treatment of trismus and include muscle relaxants, such as baclofen, nerve stabilizers such as pregabalin, and analgesics.

BTX injections can be extremely effective in treating the pain and spasms associated with radiation-induced cervical dystonia (Fig. 6). As in other disorders, BTX injections will not directly treat fixed contractures but may facilitate the progression of range of motion through physical therapy. Techniques used in the treatment of radiation-induced cervical dystonia are very similar to those used to idiopathic cervical dystonia. Clinical evaluation with particular emphasis on the patient's historical account of symptoms and physical examination are instrumental in choosing targets and dosing for therapy. As with other inductions for BTX injection, technique is often modified on subsequent injection visits to maximize efficacy.

The dose, volume, and concentration of BTX injected for radiation-induced cervical dystonia varies widely (Table 2). The most frequently injected muscles are the cervical paraspinal muscles, sternocleidomastoid, and trapezius. A "follow the pain" tactic wherein the point of maximal muscle tenderness is injected is often effective when muscles demonstrate tenderness to palpation. In muscles that are symptomatic from spasm more than pain, injection into the motor endplate zone is indicated. More than one injection point may be necessary in long or broad muscles, such as the sternocleidomastoid, to ensure maximal efficacy. Choice of needle is determined by the muscle to be injected. EMG guidance may be used when the

Cervical Injection Botulinum

Fig. 7. Injection of the mid cervical paraspinal muscles for painful radiation-induced cervical dystonia. The patient has adenocarcinoma of unknown primary metastatic to the upper cervical spine previously treated with external beam radiation. The surgical scar is from resection of a meningioma several years earlier. The lower cervical paraspinal muscles and trapezius will be injected bilaterally. The patient's spine is imaged by magnetic resonance imaging every 3 months or sooner as indicated and the imaging is reviewed before every procedure to ensure there is no significant progression of disease including paraspinal mass. Initial injections were electromyography (EMG)-guided to ensure position within contractile tissue. More comfortable non-EMG-guided injections were started once familiarity with this individual patient's anatomy was gained. A total of 200 U of botulinum toxin type A is used approximately every 6 weeks in conjunction with a nerve stabilizer (pregabalin) and narcotic (oxycodone).

Fig. 7. Injection of the mid cervical paraspinal muscles for painful radiation-induced cervical dystonia. The patient has adenocarcinoma of unknown primary metastatic to the upper cervical spine previously treated with external beam radiation. The surgical scar is from resection of a meningioma several years earlier. The lower cervical paraspinal muscles and trapezius will be injected bilaterally. The patient's spine is imaged by magnetic resonance imaging every 3 months or sooner as indicated and the imaging is reviewed before every procedure to ensure there is no significant progression of disease including paraspinal mass. Initial injections were electromyography (EMG)-guided to ensure position within contractile tissue. More comfortable non-EMG-guided injections were started once familiarity with this individual patient's anatomy was gained. A total of 200 U of botulinum toxin type A is used approximately every 6 weeks in conjunction with a nerve stabilizer (pregabalin) and narcotic (oxycodone).

anatomy is not easily palpable, when injecting near tumor or surgical scar, or when injecting around spinal stabilization hardware to ensure the needle is in contractile tissue. In most instances, a 25-gage needle 1- to 1.5-in. long is sufficient. Injections are usually repeated every 6 weeks.

Potential major complications include bleeding and infection, especially if injections are near spinal stabilization hardware or tumor. Neck drop can occur when injecting weak spinal muscles. Precipitation or worsening of dysphagia is particularly problematic because patients with RFS that involves the neck often have pre-existing difficulty. Overtreatment with BTX can result in aspiration or the need for a feeding tube.

Get Glowing Skin

Get Glowing Skin

This is a great guide that will help you with all your skin care needs to get the best looking glowing skin.

Get My Free Ebook


Post a comment