Drug Treatment for
Blepharospasm / Meige and Hemifacial Spasm

Robert B. Daroff, M.D.
University Hospitals of Cleveland

Prior to the introduction of botulinum toxin for the treatment of benign essential blepharospasm (BEB) and hemifacial spasm (HS), and the popularization of microvascular decompression of the facial nerve for HS, pharmacological therapy was the major approach for BEB and HS, and usually remains so for Meige.

In the 1960s, Dr. David Reynolds (Reynolds et al, 1967), the Chairman of Neurosurgery at the University of Miami School of Medicine, introduced bilateral differential section of the facial nerves as a treatment for BEB. With an electrical stimulator, he identified nerve branches as they exited from the stylomastoid foramen, and severed branches to all the facial muscles except for those to the platysma. Whereas the aim was only denervation of the orbicularis oculi, unless the entire face was denervated, nerves grew back, reinnervated the orbicularis oculi, and the blepharospasm recurred. When only the nerves to the platysma were unsevered, nerve sprouting ultimately innervated the lower portion of the face, leading to the return of facial expression, but generally did not reinnervate the orbicularis oculi. Thus, this surgical treatment resulted in bilateral facial diplegia that persisted for months before facial movement resumed. With this as the definitive surgery for BEB, there was strong patient motivation for drug therapy. I joined the Department of Neurology at the University of Miami in 1968, and Reynolds referred his cases to me for a drug trial before surgery. I therefore developed considerable experience with the drugs available in the late '60s and early '70s, which consisted of the anticholinergics (Artane, Cogentin et al), and levodopa. The latter was ineffectual in BEB, and the anticholinergics had only modest benefit. Fortunately, additional drugs became available.

In 1985, Dr. Linda Hershey and I reviewed all the published drug studies for the treatment of BEB/Meige (Hershey and Daroff, 1985). Most were open, unblinded studies, and the effectiveness of drugs were the same for BEB and Meige. We found the following: 1) probably less than 10% of patients experienced sustained benefit from anticholinergic agents; 2) neuroleptics may be effective but side effects and the risk of tardive manifestations precluded their general use; 3) benzodiazepines, particularly clonazepam, seemed particularly promising, with one study showing sustained benefit in 67% of patients; 4) tetrabenazine (a dopamine depleting agent) showed good results in one study and poor results in another, but since the drug is not FDA-approved, it can only be used experimentally in the U.S.; 5) dopaminergic agents (Sinemet et al) were generally not effective; and 6) baclofen was effective in 17% in one study, and 45% in another. Any evaluation of drug treatment of BEB/Meige must be tempered by the 11% spontaneous remission rate, particularly within the first five years after onset (Castelbuono and Miller, 1998).

Since this 1985 report (Hershey and Daroff, 1985), botulinum and myectomy evolved into the most popular and efficacious treatment modalities for BEB and there have not been new major drug studies. Cyproheptadine and nicotine nasal spray were anecdotally recommended, but have either been disappointing in practice (cyproheptadine) or when studied (nicotine nasal spray) (Dressler et al, 1998).

Botulinum toxin was only approved for use in Japan in 1998. Thus, Japanese physicians had greater need for finding new drugs for BEB/Meige. Ohara et al (1999) found mexiletine, a form of oral lidocaine used as a cardiac anti-arrhythmic agent, beneficial for spasmodic torticollis and, in an open study, BEB. In the latter report, all three studied patients responded; they all continued to have increased blink rates, but their forced spasmodic eye closure was substantially reduced, and the patients reported improvement in their functional state. Ohara et al started patients on 50mg t.i.d., and titrated the drug upward until maximum benefit or side effects (the more common being: heartburn, nausea, lethargy, ataxia, and tremor). The final doses in the three patients were 450, 700, and 750mg per day. Unfortunately, in the United States, the smallest preparation of mexiletine is a 150mg capsule. I recommend opening a capsule and starting at 75mg b.i.d., but only after cardiac evaluation and clearance. The Ohara et al paper was accepted for publication in August 1998, and they haven't published follow-up of their subsequent experience. However, I wrote the authors, and received a response on July 28, 2000. Botox, and not mexiletine, is covered by the Japanese National Health Insurance. Therefore, given a choice, patients always opt for Botox. Five patients who had improved on mexiletine (three of whom were in the original 1999 report) did better with Botox than mexiletine. Two of these continue to take mexiletine between Botox doses. Thus, mexiletine may be a useful adjuvant to Botox in BEB.

Occasionally, an excitingly optimistic journal article title appears, such as that by Mostofsky et al (2000), "The Control of Blepharospasm by Essential Fatty Acids". The article described dopamine-depleted rats who had rapid blink rates, that the authors felt mimicked BEB. The rats were given a three-week course of two fatty acids (linoleic and alpha-linoleic), and the blink rate returned to normal. Of interest, is that the same authors (see S. Yehuda journal articles in PubMed, 1994-2000) reported that the fatty acid preparation improves the quality of life in Alzheimer patients, raises both pain and seizure thresholds, improves learning, and reduces the effects of intense stress. I am dubious about all-purpose cure-alls.

If an exogenous toxin promotes or exacerbates a disease, avoiding or eliminating the toxin should prevent or improve the condition. Behari et al (2000) attempted to identify risk factors in 57 patients with BEB/Meige from India, compared to a control population. They eliminated any role of exposure to fumes, dust and pets; socioeconomic status; or alcohol, tea/coffee use, but did find that chewing betel nuts or tobacco were associated with the development of BEB/Meige. Moreover, the combination of chewing betel nuts and tobacco was a highly significant predictor (odds ratio of 7.4). The active ingredient in betel nuts, which are only grown in Asia, is arecoline, a muscarinic agent. Thus, patients with Meige should avoid chewing betel nuts, or at least not combine them with tobacco chewing. On the positive side, the beneficial effects of chewing betel nuts are a decrease in the severity of schizophrenia (Sullivan et al, 1990), improved memory in Alzheimer's Disease (Maiese et al, 1994), a "sense of exhilaration" and heightened sexual desire (http://www.ucalgary.ca/~chilton/Betel.htm). On the negative side, in addition to increasing the risk of BEB/Meige, betel nuts cause "red teeth" and substantially increase the risk of oral cancer (Shiu et al, 2000). The relationship among the various consequences of betel nut chewing (BEB/Meige syndrome, improved memory in Alzheimer's, decreased symptoms in schizophrenia, red teeth, oral cancer, exhilaration, and lasciviousness) will be for others to unravel.

Apraxia of eyelid opening (ALO) occurs in parkinsonian states, and in patients with BEB. With the latter, it is often vexing, as it does not respond to medication and is not consistently improved with Botox. Hirayama et al (2000) reported two patients with ALO and parkinsonism, whose ALO improved dramatically while wearing tight skiing or swimming goggles. This was due to the "sensory trick" induced by the tight-fitting goggles. Krack and Marion (1994) had reported that touching both temples helped patients with pure (without parkinsonism or BEB) ALO but didn't comment specifically on BEB patients with ALO. Goggles, which provide sustained and intense cutaneous stimulation, are worth trying in BEB patients with ALO.

Meige may be helped by botulinum but most patients also require drug therapy. For treating Meige, and as a supplement to botulinum for BEB, my drug of choice is clonazepam, which has the added benefit of being an anxiolytic in patients, whose primary symptoms tend to provoke anxiety, which is in a positive feedback loop with the movement disorder. After clonazepam, I use baclofen and Artane.

Another "exciting" journal article title was "Treatment of Meige Syndrome with ECT". The authors (Boshes et al, 1999) reported a woman whose Meige responded dramatically after bilateral electroconvulsive therapy but, unfortunately, it only lasted a few days.

BEB/Meige, in addition to being a primary idiopathic disorder, may be "tardive", meaning occurring secondary to neuroleptic (antipsychotic) drugs (Sachdev, 1998). Discontinuation, or even modest reduction in medication dose, may cause a flare-up of the psychosis. The newer atypical neuroleptics, such as clozapine, can be substituted, in the hope that the BEB/Meige will be controlled without re-emergence of the psychosis (Levin & Reddy, 2000). When atypical neuroleptics fail, gabapentin may be of benefit in schizoaffective and bipolar patients (Hardoy et al, 1999).

Prior to the popularization of microvascular decompression and botulinum, anticonvulsants such as Dilantin and Tegretol (Alexander and Moses, 1982) were the treatments of choice, followed by clonazepam (Herzberg, 1985) and baclofen (Evidente and Adler, 1998). More recently, Bandini and Mazzella (1999) showed an excellent response in five patients with gabapentin, in doses ranging from 900-1600mg qd; and Millan-Guerrero et al (2000) described three patients who experienced a 75 percent reduction over a period of four years, while taking Sinemet 25/250 b.i.d.

1. Alexander GE, Moses H: Carbamazepine for hemifacial spasm. Neurology 1982;32:286-287.
2. Bandini F, Mazzella L: Gabapentin as treatment for hemifacial spasm. Eur Neurol 1999;42:49-51.
3. Behari M, Sharma AK, Changkakoti S, Sharma N, Pandey RM: Case-control of Meige's syndrome. Neuroepidemiology 2000;19:275-280.
4. Boshes RA, Afonso JA, Tanev K: Treatment of Meige's syndrome with ECT. J ECT 1999;15:154-157.
5. Castelbuono A, Miller NR: Spontaneous remission in patients with essential blepharospasm and Meige syndrome. Am J Ophthalmol 1998;126:432-435.
6. Dressler D, Scaravilli T, Bhatia KP, Marsden CD: Nicotine nasal spray is not reliable treatment for blepharospasm: results of a pilot study. Mov Disord 1998;13:190.
7. Evidente VGH, Adler CH: Hemifacial spasm and other craniofacial movement disorders. Mayo Clin Proc 1998;73:67-71.
8. Hardoy MC, Hardoy MJ, Carter MG, Cabras PL: Gabapentin as a promising treatment for antipsychotic-induced movement disorders in schizoaffective and bipolar patients. J Affect Disord 1999;54:315-317.
9. Hershey LA, Daroff RB: Medical management of benign essential blepharospasm. Adv Ophthal Plastic & Reconstruct Surgery 1985;4:183-194.
10. Herzberg L: Management of hemifacial spasm with clonazepam. Neurology 1985;35:1676-1677.
11. Hirayama M, Kumano T, Aita T, Nakagawa H, Kuriyama M: Improvement of apraxia of eyelid opening by wearing goggles. Lancet 2000;356:1413.
12. Krack P, Marion MH: "Apraxia of lid opening," a focal eyelid dystonia: clinical study of 32 patients. Mov Disord 1994;9:610-615.
13. Levin H, Reddy R: Clozapine in the treatment of neuroleptic-induced blepharospasm: a report of 4 cases. J Clin Psychiatry 2000;61:140-143.
14. Maiese K, Holloway HH, Larson DM, Soncrant TT: Effect of acute and chronic arecoline treatment on cerebral metabolism and blood flow in the conscious rat. Brain Res 1994;641:65-75.
15. Millan-Guerrero RO, Tene-Perez E, Trujillo-Hernandez B: [Levodopa in hemifacial spasm. A therapeutic alternative] [Article in Spanish]. Gac Med Mex 2000;136:565-571.
16. Mostofsky DI, Yehuda S, Rabinovitz S, Carasso R: The control of blepharospasm by essential fatty acids. Neuropsychobiology 2000;41:154-157.
17. Ohara S, Tsuyuzaki J, Hayashi R: Mexiletine in the treatment of blepharospasm: experience with the first three patients. Mov Disord 1999;14:173-175.
18. Reynolds DH, Smith JL, Walsh TJ: Differential section of the facial nerve for blepharospasm. Trans Am Acad Ophthal Otolaryngol 1967;71:656-664.
19. Sachdev P: Tardive blepharospasm. Mov Disord 1998;6:947-951.
20. Shiu MN, Chen TH, Chang SH, Hahn LJ: Risk factors for leukoplakia and malignant transformation to oral carcinoma: a leukoplakia cohort in Taiwan. Br J Cancer 2000;82:1871-1874.
21. Sullivan RJ, Allen JS, Otto C, Tiobech J, Nero K: Effects of chewing betel nut (Areca catechu) on the symptoms of people with schizophrenia in Palau, Micronesia. Br J Psychiatry 2000;177:174-178.