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Head and Neck Muscle Spasm After Radiotherapy
Management With Botulinum Toxin A Injection
Douglas J. Van Daele, MD;
Eileen M. Finnegan, PhD;
Robert L. Rodnitzky, MD;
Weining Zhen, MD;
Timothy M. McCulloch, MD;
Henry T. Hoffman, MD
Arch Otolaryngol Head Neck Surg. 2002;128:956-959.
ABSTRACT
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Objective To introduce the concept of neck muscle pain and spasm after radiotherapy
and its treatment with botulinum toxin A.
Design Case series.
Setting Ambulatory patients at a tertiary care medical center.
Patients Individuals who had undergone primary or adjuvant radiotherapy for treatment
of carcinoma of the head and neck were asked about painful spasms of the neck
musculature. A volunteer sample was used. If they desired treatment with botulinum
toxin A, they were included in the study.
Intervention Patients received botulinum toxin A injections to the affected sternocleidomastoid
muscle(s) in 1 or 2 locations.
Outcome Measure Subjective pain relief.
Results Four of 6 patients with painful tightness of the neck who received botulinum
toxin A injections to the sternocleidomastoid muscle achieved pain relief.
Conclusions A subset of patients with irradiation-induced cervical muscle spasm
benefit from treatment with botulinum toxin A injections. Further study is
needed to more clearly define the entity and treatment.
INTRODUCTION
COMPLICATIONS FROM head and neck radiotherapy range from mild xerostomia,
dysphagia, muscle atrophy, and soft tissue fibrosis to osteoradionecrosis,
hypothyroidism, and spinal cord inflammation or necrosis. Painful chronic
bladder spasms have been reported as a consequence of radiation for cervical
carcinoma,1 and trismus has been reported as
both an acute and late complication of upper aerodigestive tract radiotherapy
with and without concurrent chemotherapy.2-4
Radiation-induced trismus due to secondary myokymia of the masseter muscle
after treatment for palatal adenocarcinoma has been treated effectively with
botulinum toxin A in the past.4 However, there
are no reports in the literature describing painful spasms of the neck musculature
after neck radiotherapy. The purpose of this study is to introduce the concept
of painful postirradiation muscle spasms of the head and neck musculature
specifically of the sternocleidomastoid muscle and the use of botulinum toxin
A to help manage the disorder.
PARTICIPANTS AND METHODS
Subjects were identified through the University of Iowa Department of
Otolaryngology–Head and Neck Surgery, Iowa City. Patients with prior
radiotherapy to the head and neck for carcinoma were asked about painful tightness
of the neck musculature. A pain rating scale was not utilized. If the patient
reported bothersome intermittent tightness and pain, he or she was offered
botulinum toxin A injection. Patients with head turning, other involuntary
movements associated with the painful tightness, or new-onset cranial nerve
deficit were excluded from this study as were those with evidence of recurrent
disease or trauma or surgery to the head or neck within the past month.
Written informed consent was obtained prior to treatment. Before the
toxin injection, local anesthetic (approximately 1 mL of 1% lidocaine with
epinephrine, 1:100 000) was infiltrated subcutaneously using a 30-gauge
needle over the sites of planned injection (Figure 1). Toxin injections were performed into the substance of
the sternocleidomastoid muscle in 2 sites using a 27-gauge Teflon needle connected
to a system specifically designed to audibly monitor electromyographic (EMG)
activity during the botulinum toxin A injection.5
The EMG system was used to confirm placement of the needle in the sternocleidomastoid
muscle and not to identify abnormal patterns of EMG activity. Palpation of
the carotid pulse was done to direct the injection away from this structure.
The patient's age, sex, original tumor site, histologic type, TNM classification,
total delivered radiation dose, number of fractions delivered, number of months
from the end of radiation treatment to diagnosis, initial dose of botulinum
toxin A injected, number of sequential injections and doses, as well as time
between injections and subjective change in pain were all determined from
the patient's chart.
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Botulinum toxin A injection sites. X indicates site of primary injections
within the sternocleidomastoid muscle belly; asterisk, site of injection may
be directed to the location of electromyography-guided contraction activity.
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RESULTS
Painful spasms of the sternocleidomastoid muscle were identified in
9 patients (3 women and 6 men) with an average age of 65 years (Table 1). Patients' complaints ranged from nondescript requests
for pain medication for "neck muscle pain" to more specific descriptions of
spasms occurring in the sternocleidomastoid muscle lasting seconds to minutes.
Eight of the 9 patients received either primary or adjuvant radiation therapy
for squamous cell carcinoma of the glottis (2), supraglottis (2), tongue (1),
tonsil (1), base of tongue (1), and unknown primary (1). One patient received
adjuvant therapy for Merkel cell carcinoma of the cheek, and 1 patient received
intra-arterial cisplatin therapy along with radiotherapy on a Radiation Therapy
Oncology Group protocol. These 8 patients received an average of 6500 rad
(65 Gy) (range, 5400-7400 rad [54-74 Gy]) of radiation to the neck in an average
of 37 fractions. The diagnosis of spasms after irradiation was made an average
of 37 months (range, 10-62 months) after completion of radiotherapy. Two patients
had prior selective neck dissections (levels II-IV) on the affected side.
The patient with an unknown primary tumor had a modified radical neck dissection
sparing cranial nerve XI on the affected side, and cranial nerve XI function
was clinically normal. This patient did not receive a toxin injection. The
1 patient with a base of tongue tumor had a modified radical neck dissection
on the unaffected side and no surgical procedure on the affected side.
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Patient Characteristics of Painful Spasms of the Sternocleidomastoid
Muscle*
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Six patients (2 women and 4 men) have been injected with botulinum toxin
A. One patient's pain was unchanged pain after injection of 25 U and was therefore
labeled as a nonresponder. This patient had very little audible EMG activity
noted when the toxin was injected. A second patient had an inadequate response
after 2 injections (25 U each injection, 3 months apart) and subsequently
deferred further injections. The remaining 4 patients have had complete relief
of symptoms after having undergone 2 injections an average of 3.4 months apart.
Initial injections averaged 22 total units to each affected muscle in 2 sites,
and subsequent injections have averaged 20 U. Two patients had bilateral involvement.
COMMENT
In early studies of radiation biology, muscle and peripheral nerves
were thought to be relatively radioresistant. It is now clear that radiation
treatment has both acute and late effects on muscles and peripheral nerves,
although late effects predominate and are dose dependent.3, 6
With one-time doses up to 3000 rad (30 Gy) and fractionated doses up to 8000
rad (80 Gy) (when the dose per fraction was <270 rad [<2.7 Gy]), animal
studies have shown few effects on muscle histologic features for the first
3 to 4 weeks after therapy. However, as early as 2 to 4 months after a one-time
2000 rad (20 Gy) treatment, focal areas of loss of capillaries with muscle
degeneration develop. Increase in collagen and decrease in proteoglycans in
the extracellular matrix follows and leads to disorganized structure and tissue
fibrosis. The effect can be progressive for up to 2 to 5 years and appears
to be related to the dose of radiation therapy. Based on data from patients
after radiation for carcinoma of the tonsil, Withers et al3
demonstrated that the incidence of severe muscle and bone complications designated
as grade III and IV by the modified Radiation Therapy Oncology Group/European
Organization Research on the Treatment of Cancer late radiation morbidity
scoring scheme continue to rise indefinitely as time from radiotherapy increases.
Grade III complications consist of severe induration or loss of tissue, severe
trismus, severe pain, self-limited necrosis, or bone exposure. Grade IV complications
consist of necrosis requiring surgery or leading to spontaneous fracture.
Mucosal complications, however, plateau after approximately 1 year. Karasek
et al7 indicated that for soft tissue sarcomas
doses above 5500 rad (55 Gy), the likelihood of late morbidity is increased.
Symptoms among patients in this study were identified 10 to 62 months
after therapy and after radiation treatment. This interval from treatment
to development of spasm is consistent with the time course for late muscular
complications to develop. The patient group received between 5400 and 7400
rad (54-74 Gy) in an average of 37 fractions, and thus are above the dosage
expected to increase the risk of complication. The ongoing muscle damage,
remodeling, and fibrosis in these patients may contribute to muscle excitability
and lack of soft tissue elasticity leading to painful spasms.
Irradiation has both acute and late effects on the peripheral nerve.
The acute, direct effects have been shown to be associated with EMG and chemical
changes. Long-term human and animal studies have shown radiation treatment
induces a decrease in Schwann cell proliferation leading to demyelination
and long-term fibrosis of the nerve fibers and the nerve sheath. This effect
has been shown to occur in dogs with single doses greater than 2000 rad (20
Gy). Demyelination is known to cause pain associated with spasm, especially
in progressive demyelinating diseases such as multiple sclerosis of which
trigeminal neuralgia and bladder spasms are common manifestations. Postirradiation
muscle spasm differs from a dystonia in that there is no abnormal involuntary
movement of a twisting and sustained nature as there is in torticollis. However,
it more closely clinically resembles myokymia, which is a disorder characterized
by muscular twitching. The diagnosis of myokymia requires EMG evidence of
continuous, irregular motor-unit discharges. Brachial and lumbosacral radiation
have been reported to induce secondary myokymia.8-9
While this clinical entity may represent a form of cervical myokymia, the
EMG data to confirm this diagnosis were not obtained as part of this study.
However, severe head and neck radiation-induced cranial nerve injury is rare.10
The addition of chemotherapy to radiation protocols does not appear
to change the late muscle effects of radiation.2, 6
Only 1 patient in this group received intra-arterial cisplatin, so the effect
of adding chemotherapy to radiotherapy on neck muscle spasms could not be
evaluated.
Relatively small doses of botulinum toxin A have been effective in treating
symptoms in this patient group. Initial doses averaged 22 U to each affected
muscle. This range is significantly smaller than the doses required to control
torticollis (75-100 U). Therefore, the injection is less likely to diffuse
to adjacent sites to impair swallowing function and other side effects of
sternocleidomastoid toxin injection. In addition, using smaller doses lessens
the likelihood of developing resistance to therapy.
In treatment of cervical dystonia, it is well established that botulinum
toxin A therapy is superior to placebo.11 Recently,
Hilker et al12 have shown that not only is
there a measureable clinical response to antispasmodic therapy, but patients'
scores on validated health-related quality-of-life instruments (EuroQol [EQ-5D]
and the Short-Form 36-Item Health Survey questionnaire [SF-36]) improve. In
general, patients with focal dystonia scored lower on initial testing than
the general population as it relates to health-related quality of life. Botulinum
toxin A therapy significantly improved the SF-36 and EQ-5D quality-of-life
scores in all but the SF-36 physical functioning, role-emotional, and general
health dimensions at the first follow-up visit (6 weeks after injection).
All dimensions returned almost to baseline at the second follow-up visit (12
weeks after injection) as might be expected based on the mechanism of action
of botulinum toxin A. Further study is needed to determine the effect of botulinum
toxin A therapy for patients with postirradiation muscle spasm on patient's
quality of life.
This study is limited by its small sample size. Further studies are
required to electromyographically characterize the muscle activity, to compare
the analgesic effect of the local anesthetic injection without the subsequent
toxin injection, and to determine the time of onset of the symptoms. Additionally,
other muscles within the radiation field (eg, trapezius, splenius, and levator)
were not targeted in this study; however, they have the potential to contribute
to painful neck spasms.
CONCLUSIONS
In this preliminary study, we have described neck muscles spasms after
radiotherapy in a small number of subjects. Two thirds (4 of 6) of patients
benefited from treatment of the affected sternocleidomastoid muscle with botulinum
toxin A therapy. More research is needed to clarify the etiology, incidence,
predisposing factors, time course of spasm development, and association with
combined chemotherapy and radiation dose dependency.
AUTHOR INFORMATION
Accepted for publication January 8, 2002.
This study was presented as a poster at the Fifth International Conference
on Head and Neck Cancer, San Francisco, Calif, July 30-August 1, 2000.
Corresponding author and reprints: Douglas J. Van Daele, MD, Department
of Otolaryngology–Head and Neck Surgery, University of Iowa College
of Medicine, 21201 PFP, 200 Hawkins Dr, Iowa City, IA 52242 (e-mail: douglas-van-daele{at}uiowa.edu).
From the Departments of Otolaryngology–Head and Neck Surgery
(Drs Van Daele, Finnegan, McCulloch, and Hoffman), Neurology (Dr Rodnitzky)
and Radiology, Division of Radiation Oncology (Dr Zhen), University of Iowa
Health Care, Iowa City. Dr Zhen is now with the Departments of Radiation Oncology
and Otolaryngology–Head and Neck Surgery, University of Nebraska Medical
Center, Omaha.
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