Title | Chemomyectomy of the Orbicularis Oculi Muscles for the Treatment of Localized Hemifacial Spasm |
Creator | Jonathan D. Wirtschafter, MD |
Affiliation | Department of Ophthalmology, University of Minnesota Medical School, Minneapolis |
Abstract | OBJECTIVE: To report our experience with doxorubicin chemomyectomy as an alternative to other treatments for hemifacial spasm (HFS). DESIGN: A prospective, open study Phase I clinical trial of chemomyectomy. SETTING: A hospital-based, referral neuro-ophthalmology and oculoplastic service. PATIENTS AND METHODS: Repeated (1-6, median: 4) local injections of doxorubicin were given in the eyelids of 8 patients (5 men, 3 women, average age: 71). MAIN OUTCOME MEASURES: Eyelid strength, self-reported spasm, and duration of improvement without seeking additional or alternative treatments. RESULTS: Chemomyectomy resulted in permanent (> or = 2.5 years) orbicularis oculi weakness and relief from spasms in the treated areas in 5 patients, although 2 patients requested occasional supplementary botulinum toxin (BT) injections in the facial muscles over the cheek. One patient had a successful result for 3 years, after which spasm recurred. One patient maintains a successful result in the eyelid but had a failed microvascular decompression in the lower face. One incompletely treated patient required microvascular decompression following spread of spasms to the lower branches of the facial nerve and increased severity of the HFS. One patient required eyelid surgery because of concurrent spastic entropion. One patient treated with a higher concentration than currently used required closure of a skin ulcer. CONCLUSIONS: Doxorubicin chemomyectomy is an effective alternative to conventional therapy for properly selected patients affected by HFS, particularly older patients with relatively localized eyelid muscle spasms. The modified technique of doxorubicin chemomyectomy has developed to the point where its safety is demonstrated and its risks are known. |
Subject | Older people; Older people, 80 and over; Blepharospasm/drug therapy; Doxorubicin/administration & dosage; Doxorubicin/therapeutic use; Eyelids/drug effects; Eyelids/innervation; Facial Muscles; Female; Humans; Male; Middle Older people; Muscle Denervation/methods; Oculomotor Muscles; Prospective Studies; Spasm/drug therapy |
OCR Text | Show Journal of Neuro- Ophthalmology 14( 4): 199- 204, 1994. © 1994 Raven Press, Ltd., New York Chemomyectomy of the Orbicularis Oculi Muscles for the Treatment of Localized Hemifacial Spasm Jonathan D. Wirtschafter, M. D. Abstract: Objective: To report our experience with doxorubicin chemomyectomy as an alternative to other treatments for hemifacial spasm ( HFS). Design: A prospective, open study Phase I clinical trial of chemomyectomy. Setting: A hospital- based, referral neuro- ophthalmol-ogy and oculoplastic service. Patients and Methods: Repeated ( 1- 6, median: 4) local injections of doxorubicin were given in the eyelids of 8 patients ( 5 men, 3 women, average age: 71). Main Outcome Measures: Eyelid strength, self-reported spasm, and duration of improvement without seeking additional or alternative treatments. Results: Chemomyectomy resulted in permanent ( 3= 2.5 years) orbicularis oculi weakness and relief from spasms in the treated areas in 5 patients, although 2 patients requested occasional supplementary botulinum toxin ( BT) injections in the facial muscles over the cheek. One patient had a successful result for 3 years, after which spasm recurred. One patient maintains a successful result in the eyelid but had a failed microvascular decompression in the lower face. One incompletely treated patient required microvascular decompression following spread of spasms to the lower branches of the facial nerve and increased severity of the HFS. One patient required eyelid surgery because of concurrent spastic entropion. One patient treated with a higher concentration than currently used required closure of a skin ulcer. Conclusions: Doxorubicin chemomyectomy is an effective alternative to conventional therapy for properly selected patients affected by HFS, particularly older patients with relatively localized eyelid muscle spasms. The modified technique of doxorubicin chemomyectomy From the Departments of Ophthalmology, Neurology, and Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota, U. S. A. This work was supported in part by Minnesota Lions and Lionesses, an unrestricted grant from Research to Prevent Blindness, Inc., New York City, NY, the Frank E. Burch Chair in Neuro- Ophthalmology and NEI grant # R01 EY 07935. Address correspondence and reprint requests to Dr. Jonathan D. Wirtschafter, Department of Ophthalmology, University of Minnesota, UMHC Box 493, Minneapolis, MN 55455- 0501, U. S. A. has developed to the point where its safety is demonstrated and its risks are known. Key Words: Hemifacial spasm- Blepharospasm- Doxorubicin- Orbicularis oculi myectomy- Chemomyectomy. Hemifacial spasm is a chronic condition causing contraction of the eyelids and other muscles innervated by the facial nerve. It can be a cause of significant disability, forcing changes in the patient's work or lifestyle. This paper describes our experience with doxorubicin chemomyectomy and compares three alternative treatments for hemifacial spasm ( HFS): surgical microvascular decompression with the goal of permanent relief ( 1- 3), chemodenervation with injections of botulinum A toxin ( BT) for temporary relief ( 4- 6), and surgical orbicularis myectomy ( 7,8). Most cases are due to microvascular compression of the facial nerve at its root exit zone near the brainstem. In an effort to provide a more permanent form of treatment for orbicularis oculi spasm, doxorubicin chemomyectomy was developed. The procedure takes advantage of the myotoxicity of doxorubicin in skeletal muscles. Doxorubicin chemomyectomy has developed on the basis of a continuing and extensive series of laboratory investigations ( 9- 12). Our clinical experience through May 1990 in patients with benign essential blepharospasm and HFS has been reported ( 13). In reviewing our experience to March 1994, we have had more success in completion of the protocol with patients whose diagnosis was HFS than in those with benign essential blepharospasm. We believe the data reported here serves as the basis for recommending doxorubicin chemomyectomy as an alternative therapy to selected patients with relatively localized ocular muscle spasm as a part of HFS. 299 200 /. D. WIRTSCHAFTER PATIENTS AND METHODS Chemomyectomy was performed in eight patients ( 5 men, 3 women, average age: 71 years) with hemifacial spasm with approval from the University of Minnesota Committee on the Use of Human Subjects in Research and a Phase I clinical trial authorized by the United States Food and Drug Administration. Informed consent was obtained from the patients. All patients had had reasonably effective responses to botulinum A toxin, but were desirous of having a response lasting longer than 3 months. We excluded patients who had recent myocardial infarction, cardiomyopathy, cardiac arrhythmia, congestive heart failure, bone marrow depression or other hematologic abnormalities, kidney or liver failure, pregnancy or the substantial possibility of future pregnancy, unexplained alopecias, especially of the eyelids, non- Causacians in whom treatment could result in pigment loss, persons with unwrinkled eyelid skin in whom scarring would be highly evident, and persons with impaired eyelid function, corneal ulcers, keratitis, or dry eyes. Eyelids with insufficient prior orbicularis myectomies were also excluded. Laboratory studies were obtained at the time of the first injection and repeated at approximately 1- year intervals if injections continued. The studies and required values were as follows: hemoglobin ( between 11.0 and 15.5 g/ dl), leukocyte count (> 3,500/ mm3), aspartate aminotransferase ( AST) (< 33 units). We reported previously ( 13) concerning chemomyectomy for all forms of eyelid spasms. This study began in April 1988. The present report was prepared because the results with HFS are presently better defined than those with benign essential blepharospasm. There had been two changes in the protocol during the study. Patients were always treated with the then- current protocol. Three patients in the present study received initial doses of doxorubicin at a concentration of 2 mg/ ml or in varying lower concentrations when low doses were given. Subsequent to January 1991, all our patients received all doses at a concentration of 1 mg/ ml in 0.9% sodium chloride solution. The doxorubicin was injected into the presumed orbicularis oculi layer of the eyelids using a 30- gauge 5/ 8- inch needle. Any doxorubicin solution that spilled on the eyelids or ocular surface was completely irrigated with water or saline solution, respectively. The second change in the protocol that affected all but one of the patients in this study was instituted in January 1990, when a preinjec-tion of 5 ml of 0.5% bupivacaine containing 1/ 100,000 epinephrine and 150 units of hyaluroni-dase ( Wydase) preceded the injection of doxorubicin by 20- 30 minutes. If both upper and lower eyelids were treated at the same visit, each lid received a 5- ml injection. This preinjection solution had proved useful in animal models, increasing the proportion of orbicularis oculi muscle fibers destroyed ( 14). Eight patients ( five males, three females), ages 55 to 81 years, were treated with increasing doses ( 0.8 mg to 1.5 mg) of doxorubicin injected into one or two eyelids with a 3- month minimum reinjec-tion interval for each site. This resulted in cumulative doses of 0.8 to 7.0 mg doxorubicin. There were three main outcome measures: eyelid strength, self- reported spasm, and " improved days." The strength of all eyelids was graded from 0 to 4: 0 indicated complete flaccidity, and 4 indicated the patient could voluntarily " bury the base of the eyelashes" and could overcome any effort to force the eyelids open. Spasm as described by the patient was also graded from 0 to 4 according to the procedure of the clinical investigation of botulinum toxin as performed by Scott: 0 = none; 1 = increased blinking caused by external stimuli; 2 = mild noticeable fluttering, not incapacitating; 3 = moderate noticeable spasm, mildly incapacitating; 4 = severely incapacitating, unable to read, write, drive, etc. The use of the self- reporting spasm intensity scale was problematic, except when the spasms were almost completely absent in the entire face. The patient was asked to report spasms in the treated eyelids only. The improvement rating is obtained by subtracting the final posttreatment spasm from the initial. We thus developed another scale, " Improved Days," which is defined as the interval between the most recent examination or interview patient encounter and the patient's most recent doxorubicin injection, during which time the patient reported improvement of spasm and did not receive subsequent orbicularis myectomy, neurovascular decompression surgery, nor botulinum A toxin injections to the treated area. In order to be counted as " improved," the patient's self-reported spasm in the treated area had to have been 2 or greater, and at least 180 days had to have passed since the patient's most recent doxorubicin injection. All patients in the presently reported series have now been followed at least 18 months since their last injection of doxorubicin and are considered tentative " cures." Our comments on the indications for surgical myectomy are based on a series of four women ( average age: 70 years) with HFS and age- related dermatochalasis of the eyelids treated with unilateral upper and lower eyelid or- / Neuro- Ophthalmol, Vol. 14, No. 4, 1994 CHEMOMYECTOMY FOR HEMIFACIAL SPASM 201 bicularis myectomy on the side of the HFS, combined bilateral upper eyelid blepharoplasties with correction of eyelid and eyebrow ptosis as needed. RESULTS Each doxorubicin injection was followed by 1 to 8 weeks of local swelling and/ or bruising of the tissue. Sometimes the black, blue, and yellow discoloration would extend as far down as the angle of the mandible. The injected area was tender to touch but not spontaneously painful until healing occurred. The data for the HFS patients treated with chemomyectomy is summarized in Table 1. All of the patients have been followed for more than 2.5 years since the last doxorubicin injection. Five of these patients have not had any subsequent treatment and are tentatively regarded as " permanent" cures. One of the patients ( No. 13) had a successful result for 3 years but now reports that she is " almost as bad as before treatment." She plans to seek reevaluation and treatment. One patient ( No. 11) maintains a successful result from the chemomyectomy but in October 1992 had microvascular decompression seeking to stop the spasms in her lower face. After 8 months of initial success, the spasms recurred to about 50% of their prior intensity. The eyelid spasm became less active at the time of the decompression and returned to its prior mild intensity with the recurrence. The strength of the eyelids was between 1 and 2 on a scale of 0 to 4. The success of the chemomyectomy in the treated areas is demonstrated by the fact that botulinum A toxin injection of the eyelids was not requested by those two patients who have chosen to have an occasional botulinum toxin injection in the upper cheek to relieve lower facial spasms, even though eyelid injection would have been performed at little or no additional cost or inconvenience. Most of the patients have some residual hemifacial spasm. Some have mild- to- moderate spasm in their lower face, but they do not find it as debilitating as the intermittent closure of their eyes. Doxorubicin injections can cause loss of subcutaneous fat and contracture and scarring of connective tissues within the eyelid, including the orbital septum. In some patients the doxorubicin injections can produce a " chemical" blepharoplasty ( Fig. 1) with an apparent tightening of the eyelids, and this can be aesthetically pleasing, especially if there is an elevation of the upper eyelid fold. The lid may also appear pinker long after the acute inflammation has resolved. The eyelid may feel tight, scarred, or lumpy. Conversely, doxorubicin may produce an unwanted dimple on the cheek with loss of fat over the zygomatic arch following injection in this location. This limits the usefulness of chemomyectomy in the lower zygomatic and buccal branches of the facial nerve. We have not experienced any full- thickness skin ulcers since the concentration of the doxorubicin was reduced from 2.0 to 1.0 mg/ ml. Since then patients have noticed transient blisters that cleared before they returned for scheduled appointments. One patient with HFS ( No. 18) developed a 1- cm ulcer on his cheek at an injection site when a concentration of doxorubicin of 2.0 mg/ ml was used. This patient required two repairs, as the first excision was not sufficiently large, and he reports continuing discomfort in that area. He is, however, satisfied with his result. One chemomyectomy pa- TABLE 1. Improvement and sequellae following doxorubicin chemomyectomy for hemifacial spasm Pt. no. 14 18 16 13 11 17 20 12 Sex M F M F F M M M Age 61 81 77 77 55 73 66 78 Cum'l DXR dose ( mg) 7.00 6.60 5.50 4.60 4.20 4.00 4.00 0.80 Improvement 0- 4" 3 4 4 4 4 3 2 0 Total no. DXR inj 6 4 4 4 4 2 2 1 ( Upper lid 1.0( 1) 2.0 ( 2) 1.4( 2) 0 1.0( 1) 1.0( 1) 1.0( 1) 0 Sum'l DXR dose, mg ( no. of Inh Lateral canthus 0.6 ( 2) 0.5 ( 2) 0.3( 1) 1.2( 1) 1.0( 1) 0.7 ( 2) 0.3( 1) 0 Lower lid 2.7 ( 4) 3.3 ( 3) 1.3( 1) 2.0 ( 2) 2.2 ( 2) 2.3 ( 2) 1.2( 1) 0.8( 1) Cheek 2.7 ( 4) 0.8( 1) 2.5 ( 2) 1.4( 1) 0 0 1.5( 1) 0 Date of last DXR 2/ 18/ 91 7/ 21/ 91 7/ 16/ 91 2/ 12/ 90 3/ 12/ 90 10/ 1/ 90 12/ 17/ 90 4/ 17/ 89 Date of last post- DXR BTInj of cheek 4/ 12/ 93 6/ 29/ 92 Improved daysb 1128 975 980 1134° 1471 1268 0 0 Subsequent surgery Failed NeuroV Decomp. 10/ 92 for lower face Ulcer repair 2/ 91, 11/ 91 NeuroV Decomp 4/ 91 DXR, doxorubicin; Cum'l, cumulative; Pt, patient; Inj, injection; BT, Botulinum A toxin; NeuroV, neurovascular; Decomp, decomposition. " Improvement rating: initial degree of spasm minus the degree of spasm reported at the last patient encounter. b Improved days: see text for definition. ° Late failure after 3 years. / Neuro- OphtMmol, Vol. 14, No. 4, 1994 202 /. D. WIRTSCHAFTER DISCUSSION FIG. 1. Chemomyectomy patient 18 at 22 months after her final injection for left hemifacial spasm. Note that the left eyelid fissure is slightly larger than the right. The loss of subcutaneous fat and the tightened appearance of the orbital septum of both the left upper and lower lid can be compared with that of the right upper and lower lids, respectively. Note also that the upper eyelid fold is raised approximately 5 mm. General appearance is similar to that which results following a cosmetic blepharoplasty. tient with blepharospasm ( not included in this series) had a lower lid cicatricial ectropion that did not lead to any corneal injury but did require a skin graft for its relief. One patient ( No. 20) was incompletely treated with 4.0 mg doxorubicin when there was an abrupt enlargement in the pattern of his HFS. His mouth and platysma muscle became very severely involved, and he was unable to continue his work as a school principal with this degree of abnormality. He had successful neurovascular decompression, albeit with a temporary complete facial nerve paralysis. Patient 12 was known also to have a spastic entropion in addition to HFS. His one injection of doxorubicin ( 0.8 mg) produced edema and swelling of the lower lid so that the lashes were striking the cornea. This patient required taping of the lower lid and the insertion of ointment to protect this cornea. He subsequently had plastic surgery elsewhere, which was sufficient to both relieve the spastic entropion and HFS of the lower lid for his remaining 3 years of life. All patients have a somewhat increased ( 1- 2.5 mm) vertical eyelid aperture on the treated side that results from the weakening of the orbicularis oculi muscle. We did not perform Schirmer tests for tear output, but there was no evidence that the conjunctival glands are injured in any way. Because of weakened eyelid closure some patients may need to use ocular lubricants when external conditions ( e. g., low humidity, high wind velocity) promote dry eye symptoms. This study suggests that doxorubicin chemomyectomy is a reasonably safe and effective treatment for localized HFS when it most symptomatically involves the orbicularis oculi muscle or for treatment of patients with more generalized HFS who would be satisfied with relief of the ocular component of their symptoms. No patient was discontinued from the study on the basis of systemic toxicity or change in the baseline laboratory tests that were repeated yearly. No evidence of local precancerous skin changes was observed clinically nor in the one doxorubicin- treated blepharospasm patient whose eyelids were subsequently biopsied ( 15). Table 1 summarizes the doses used and helps to establish guidelines for treatment. The important parameters are the cumulative dose required for an adequate response in each lid and the maximum dose that can be delivered at one injection. The duration of treatment is a function of the number of doses required. Relief occurred following 1 to 6 injections ( median: 4). The maximum cumulative dose of doxorubicin required for improvement in a single patient was 7 mg, and the minimum was 4 mg, delivered in two to six injection sessions. The minimum cumulative effective dose for an upper eyelid was 1.0 mg and the maximum cumulative dose used as 2.0 mg, while for the lower eyelid, the minimum cumulative effective dose was 1.3 mg and the maximum cumulative dose used was 2.7 mg. The maximum dose on a single occasion was 1.0 mg for the upper lid and 1.3 mg for the lower lid. The eyelid protractors in the adjacent lateral canthal region were often simultaneously injected with either the upper or lower eyelid. The maximum cumulative dose in the lateral canthal region was 1.2 mg, and a typical low dose was 0.3 mg injected on each of two occasions. The maximum cumulative dose for injection in the cheek was 2.7 mg with the maximum on one occasion of 1.5 mg. The cheek and lower eyelid should not be injected simultaneously to prevent excessive local tissue reaction that could lead to cicatricial ectropion. Cheek doses may cause atrophy of the subcutaneous fat and create an unaesthetic dimple or crater over or below the zygomatic arch. We do not recommend the use of doxorubicin chemomyectomy for patients who do not meet the inclusion and exclusion criteria stated above. We specifically exclude young patients because the teratogenic and carcinogenic potential of doxorubicin is unknown, although the drug has a relatively short half- life as an intact compound, which per- / Neuro- Ophthalmol, Vol. 14, No. 4, 1994 CHEMOMYECTOMY FOR HEMIFACIAL SPASM 203 haps limits the exposure to the drug. We have no experience injecting non- Caucasians where depigmentation of the eyelid skin may be an unacceptable side effect. The prolonged postinjection appearance has been the major deterrent to completion of the required series of injections. Because only half the number of injections are required by patients with HFS than patients with essential blepharospasm, patients with HFS tend to complete the series of injections with fewer interruptions. After the completion of treatment, the treated eyelids are less flaccid, pinker ( due to loss of subcutaneous tissue), and younger- looking ( presumably due to increased density of the connective tissue or loss of preseptal and subcutaneous fat) than the opposite lid ( Fig. 1). We have not yet broached the subject of a balancing " chemical blepharoplasty" of the opposite eyelids. To justify the " improved days" outcome measure, we note that except for microvascular decompression, none of the treatment modalities discussed can offer the patient the reward of total, permanent cure if it is successful. All of the other treatments are a compromise involving the patient's evolving perception of the risks, costs, and benefits of the alternative treatments. Thus we believe the recording of " improved days" following chemomyectomy is a valid measure of the patient's perception that the treatment has an optimal result beyond which no other treatment is worth pursuing. The reasons for patients dropping out of a clinical trial include reasons related to the disease ( discouragement and/ or failure to appreciate any improvement), the medication ( adverse reaction or unpleasant properties), the clinical trial itself ( loss of interest or onerous requirements) and others ( moving away, discouragement by friends or family, intercurrent illness) ( 16). All of these factors were identified as operative during this clinical trial. However the choice by patients to return and not have botulinum A toxin treatment in the chemomyectomy- treated areas should be taken at face value, especially when the two patients chose to have botulinum A toxin injected in adjacent nontreated cheek areas. These patients are not dropouts from the study and serve to validate the " improved days" methodology. We would accept as a valid criticism that we did not use a " masked questionnaire" or a disinterested party to perform the interview, although intake interviews on the return visit are performed by a nurse who is not rewarded for reporting successful results. In regard to those blepharospasm patients who have dropped out because of pressure from friends or family, the main reason was the bruised appearance of the face and the suggestion that this was the result of an attack by the patient's husband. This became such a recurrent theme that we have designed a large button for the patient to wear with a cartoon and caption " The Doctor Did It!" While no patient in the hemifacial spasm chemomyectomy series required an ectropion repair for an injection complication, one patient in our trial blepharospasm series did require such a repair. These surgical repairs are relatively minor but do add to the cost and must be considered in advising the patient concerning risks and benefits. One patient ( No. 17) had pain associated with an ulcer at the injection site over the zygomatic arch. Table 2 compares and contrasts four alternative treatments for HFS. The comparisons are general and application to each patient must be individualized. Both chemomyectomy and surgical myectomy could be considered for patients over 50 years of age. We have not yet performed doxorubicin chemomyectomy in patients younger than 50, but there is no absolute contraindication. Surgical myectomy resolves concurrent problems associated with the aging eyelid, particularly ptosis, which can be repaired simultaneously. Conversely, ptosis may be recurrently exacerbated by botulinum A toxin injection in some patients even when the dose is reduced and the injection given at the eyelash base in order to be as far away as possible from the levator palpebrae superioris muscle. The complete paralysis induced by botulinum toxin injection in the lower eyelids of young patients is welcome but the lack of any muscle tone can cause severe symptomatic paralytic ectropion in the aged eyelid. In this circumstance the lesser degree of paralytic ectropion produced by chemomyectomy and surgical myectomy can be helpful. Both of the myectomies may lead to cicatricial ectropion that may require correction. None of the three other treatments preclude subsequent use of botulinum toxin. The myectomies allow the botulinum toxin to have increased effect due to decreased baseline muscle strength in the myecto-mized eyelid. The cumulative cost estimates ( Table 2) considered factors including the economic value of the time expended by the patient as well as health care professional, cost of drugs, operating room, hospital charges, and the cost of any secondary surgeries that may be required. Table 2 may be helpful in explaining the alternative therapies to the patient. In estimating that the cumulative cost associated with botulinum toxin therapy is the highest ( 4 + ) on the scale, we have allowed for only one / Neuro- Ophthalmol, Vol. 14, No. 4, 1994 204 /. D. WIRTSCHAFTER TABLE 2. Comparison of alternative treatments for hemifacial spasm Branches of facial nerve treated Patient age Indications Orbicularis weakness induced Potential complications/ exacerbated problems Result duration Secondary surgery ( if required) Subsequent BT treatment Cumulative cost Microvascular decompression All All Spasm and paresis None ( usually) Unilateral permanent facial paralysis or deafness; surgical mortality/ morbidity 90% permanent Repeat usually successful Effective + + + Botulinum toxin injection Zygomatic, buccal All Spasm Complete Ectropion, periodic dry eye, ptosis, diplopia Temporary 2- 4 months + + + + Doxorubicin chemomyectomy Zygomatic > 50 Spasm Incomplete Less ectropion than with BT, dry eye Permanent (?) Ectropion or skin ulcer repair Increased effectiveness + Unilateral surgical myectomy and bilateral blepharoplasties Zygomatic > 50 Spasm, dermatochalasis, ptosis Incomplete Less ectropion than with BT, dry eye Permanent (?) Revision, ectropion repair Increased effectiveness + + BT, botulinum A toxin. decade of treatment. In descending order of cumulative cost, the other therapies are ranked as follows: neurosurgical microvascular decompression, orbicularis oculi myectomy combined with other oculoplastic procedures, doxorubicin chemomyectomy combined with botulinum toxin therapy until a satisfactory result has been obtained. Clearly there is a role for the local treatment of hemifacial spasm with orbicularis oculi chemomyectomy in appropriately selected patients. REFERENCES 1. Janetta PJ, Abbasy M, Maroon JC, et al. Etiology and definitive microsurgical treatment of hemifacial spasm: operative techniques and results in 47 patients. / Neurosurg 1977; 47: 321- 8. 2. Moller AR, Janetta PJ. Monitoring facial EMG responses during microvascular decompression operations for hemifacial spasm. / Neurosurg 1987; 66: 681- 5. 3. Sprick C, Wirtschafter JD. Hemifacial spasm due to intracranial tumor: an international survey of botulinum toxin investigators. Ophthalmology 1988; 95: 1042- 5. 4. Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol 1985; 103: 347- 50. 5. Dutton JJ, Buckley EG. Long- term results and complications of botulinum A toxin in the treatment of blepharospasm. Ophthalmology 1988; 95: 1529- 34. 6. Garland PE, Patrinely JR, Anderson RL. Hemifacial spasm: results of unilateral myectomy. Ophthalmology 1987; 94: 288- 94. 7. Jordan DR, Patrinely JR, Anderson RL, Thiese SM. Essential blepharospasm and related dystonias. Surv Ophthalmol 1989; 34: 123- 32. 8. Frueh BR, Musch DC, Bersani TA. Effects of eyelid protractor excision for the treatment of benign essential blepharospasm. Am } Ophthalmol 1992; 113: 681- 6. 9. Baker L, Wirtschafter JD. Experimental doxorubicin myopathy: a permanent treatment for eyelid spasm? Arch Ophthalmol 1987; 105: 1265- 8. 10. McLoon LK, Wirtschafter JD. Doxorubicin chemomyectomy: injection of monkey orbicularis oculi results in selective muscle loss. Invest Ophthalmol Vis Sci 1988; 29: 406. 11. McLoon LK, Bauer G, Wirtschafter JD. Quantification of muscle loss in the doxorubicin- treated orbicularis oculi of the monkey. Invest Ophthalmol Vis Sci 1991; 32: 1667- 73. 12. McLoon LK, Ekern M, Wirtschafter JD. Verapamil substantially increases the chemomyectomy effect of doxorubicin injected into rabbit or monkey eyelid. Invest Ophthalmol Vis Sci 1992; 33: 3228- 33. 13. Wirtschafter JD. Clinical doxorubicin chemomyectomy: an experimental treatment for benign essential blepharospasm and hemifacial spasm. Ophthalmology 1991; 98: 357- 66. 14. McLoon LK, Bauer G, Wirtschafter JD. Increased tissue infiltration increases doxorubicin chemomyectomy in orbicularis oculi. Invest Ophthalmol Vis Sci 1990; 31: 43. 15. McLoon LK, Wirtschafter JD, Cameron JD. Doxorubicin injections in the eyelids of a blepharospasm patient result in significant muscle loss: a histologic examination. Am } Ophthalmol 1993; 116: 646- 8. 16. Spilker B. Guide to clinical trials. New York: Raven Press, p. 239, 1991. / Neuro- Ophthalmol, Vol. 14, No. 4, 1994 |
Date | 1994-12 |
Language | eng |
Format | application/pdf |
Type | Text |
Publication Type | Journal Article |
Collection | Neuro-Ophthalmology Virtual Education Library: Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/ |
Publisher | Lippincott, Williams & Wilkins |
Holding Institution | Spencer S. Eccles Health Sciences Library, University of Utah |
Rights Management | © North American Neuro-Ophthalmology Society |
ARK | ark:/87278/s6z63v33 |
Setname | ehsl_novel_jno |
ID | 224529 |
Reference URL | https://collections.lib.utah.edu/ark:/87278/s6z63v33 |