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Facial Dyskinesias
Facial Dyskinesias DAVID M. KAUFMAN. M.D.
The face is prominently or exclusively involved in several involuntary movement disorders. called "facial dyskinesias," in addition to the common buccolingualform oftardive dyskinesia. This review describes the appearance ofthe mostfrequently occurring facial dyskinesias: chorea, dystonia. tremor, and tics. Some new treatments are discussed.
nvoluntary movements (dyskinesias) of the face, particularly tardive dyskinesia (TO), are known to be associated with long-tenn neuroleptic use. However, it is less well known that several other neurologic conditions are also characterized by facial dyskinesias. These conditions occur commonly and can be mistaken for a psychogenic disorder or incorrectly assumed to be a manifestation of TO. Some of these other dyskinesias can be associated with dementia and appear at first to be a psychiatric disorder. Because electrophysiologic measurements, e.g., electromyograms, are usually not practical and pharmacologic tests are inconsistent,l-4 facial dyskinesias must be diagnosed almost entirely by their clinical features. In general, they become worse with anxiety and fatigue, are suppressed by concentration, and, with several exceptions, are not present during sleep. While psychiatric disturbances are common in TO and cognitive impainnents are often found in varieties of chorea, most facial dyskinesias are not consistently associated with mental aberrations. s In only a few conditions are there distinctive pathologic changes in the nervous system. Several varieties of facial dyskinesias are discernible; in this review, I will use the common orofacial or buccolingulomasticatory fonn ofTO as the reference point. The important clinical aspects ofTO and other facial dyskinesias are the movement's pattern and rapidity, the area of facial involvement, and the presence ofneck, trunk, and pelvic (axial) or limb (appendicular) involve-
I
VOLUME 30 • NUMBER 3 • SUMMER 1989
ment. By considering these aspects, the clinician can diagnose chorea, dystonia, tremor, and tics (Table I). CHOREA Bodily movements in chorea are rapid, variable, and jerky but relatively simple and nonstereotyped. At times, the movements can appear to be confluent and incessant. Chorea is the predominant dyskinesia of TO and also of choreoathetosis, Huntington's disease, Sydenham's chorea, and senile facial dyskinesia and its varieties. In its early phases and throughout most of its course, TO consists primarily or exclusively of chorea of the tongue, lower face, and jaw. It causes chewing, pouting, sucking, and vennifonn (thrusting) movements of the tongue. 6 It sometimes causes the eyelids to blink severely enough to constitute blepharospasm. 1 TO can be complicated by speech and respiratory disruptions8 similar to those associated with Gilles de la Tourene's syndrome. In advanced cases, the appendicular or axial muscles are affected. Compared to other dyskinesias, TO usually causes linle functional impainnent. Received May 25, 1988; revised August 26, 1988; accepted September 14, 1988. Address reprint requests to Dr. Kaufman, Depanment of Neurology, Montefiore Medical Center, Albert Einstein Col1ege of Medicine, III East 21 Oth Street, Bronx, N.Y., 10467. Copyright © 1989 The Academy of Psychosomatic Medicine.
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Facial Dyskinesias
TABLE 1. Cbaracteristic:s 01 facial dyskinesia Regions Involved"
Pattemsof Dyskinesia Movement Chorea
Upper Face
nonstereotype
Examples tardive dyskinesiab ++ choreoathetosis ++ Huntington's disease ++
"jerky"
Sydenham'schorea
asymmetric.
Lower Vertical Associated Face Tongue Neck Axis Limbs Dementia ++++
++++
++
++ ++ ++
++ ++ ++
++ ++ ++ ++
++
+++
+++
+
++ +++
+ ++
+++ +++
++++ ++++
++++ ++++
+++
+++
+++
+ ++ ++ ++
+ +++ ++ ++
No No· Yes No
senile/edentulous chorea
Dystonia
Tremor
Tic
generalized or focal, sustained, and predominantly twisting
torsion dystoniac ++ Wilson'sdiseasec +++ d blepharospasm ++++ Meige's syndromed ++++ hemifacial spasmd ++++ tardive dystonia" ++
Yes
++++ ++++f ++
regular, oscillatory at 2 to 12 vibrations per second
essential tremor rabbit syndrome
++++
stereotyped, forceful, irregular, rapid
simple motor tics ++++ Tourene's syndrome ++++
++++ ++++
++
+++ +++
++ ++
No Yes No No No No
++++
No No
++ ++
No No
"Involvement: rare (+); occasional (++); usual (+++); or constant (++++) "Buccolingulomasticatory variety COeneralized variety dt:ocaJ variety "Mental retardation often present fUnilateral involvement
Choreoathetosis is a dyskinesia that consists of chorea superimposed on slow, twisting, and unsustained movements (athetosis). Because choreoathetosis is almost always a congenital disorder resulting from a birth or neonatal injury, such as kernicterus, it is a stable, nonprogressive movement disorder associated with mental retardation, seizures, and spasticity. Although choreoathetosis is typically most prominent in the face, tongue, and neck, where muscles become hypertrophied, it also involves virtually all muscle groups. It often causes terrible functional incapacities, including dysarthria, hand incoordination, and walking difficulties. Unlike the facial dyskinesias of TO, those of choreoathetosis are congenital, continual. writhing, and abrupt. Moreover, they are almost always found in the presence of vocal, axial, and appendicular dyskinesias. 264
Both Huntington's disease and Sydenharn's chorea, two otherwise entirely different disorders, can present with facial chorea. In both conditions, grimacing, tongue protrusion, chewing, puckering, and other facial dyskinesias occur frequently. The facial dyskinesias in these forms of chorea, but not in TO, are almost always accompanied by appendicular and limb chorea, and the voice develops a lilting quality. Huntington's disease also induces dementia that is usually detectable when the chorea appears. A variety of Huntington's disease called "juvenile Huntington's disease" can develop in children. Affected children develop a rigid body posture with an absence of, rather than an excess of, facial movements.9-11 Their appearance mimics naturally occurring or neuroleptic-induced parkinsonism. In a major medical advance, a marker for Huntington's disease has been isolated on chromosome PSYCHOSOMATICS
Kaufman
4 12; in many cases, the marker has permitted the identification of presymptomatic heterozygote individuals and patients homozygotic for Huntington's disease. Individuals at risk ofdeveloping the disease can also be tested to determine if they are carrying the gene. Sydenham's chorea, a major manifestation of rheumatic fever, affects older children and adolescents. 13 It causes dyskinesias that can mimic tics, hyperactivity, or dyskinesia that develops upon neuroleptic withdrawal. 7 However, it does not cause permanent cognitive or personality changes. Senile facial dyskinesia involves the lower face, jaw, and tongue. Like TO, it produces sucking, lip smacking, and other oral movements that are repetitive but not rhythmic. 14 Reported incidence has ranged from 1.5% in patients older than 66 years lS to 29% in a study of retirement-home patients who were older than 59 years and who had no neurologic complaints.14 The incidence is greater in women and in patients with dementia (38%), but it does not increase with increasing age. 14 Similar dyskinesias have been found in 17% of Alzheimer's disease patients;6 and in schizophrenic patients who had not been exposed to neuroleptics. '7 These movements usually cause .little functional impairment; however, when treatment is necessary, dopamine-blocking neuroleptics reduce or suppress the movements. 14.18 A variation of senile dyskinesia, edentulous dyskinesia or orodyskinesia. occurs in elderly
edentulous individuals. Koller l9 found that 16% of 75 edentulous people had facial dyskinesias, compared with none of the controls. Although this disorder can include an element of dystonia, the movements are essentially indistinguishable from senile facial dyskinesia. 20 Compared with TO, edentulous dyskinesia involves less extensive tongue protrusion and a striking absence of upper-face and other body-area movement. 19 Properly fitting dentures correct this problem. 20 Chorea can be a manifestation of more than a dozen neurologic and general medical conditions,21 including pregnancy22 and systemic lupus erythematosus.23 Types of chorea that mimic TO in both clinical appearance and possible bioVOLUME 30. NUMBER 3· SUMMER 1989
chemical abnormalities can result from many medications besides the well-known antipsychotic preparations. Such medications include tricyclic antidepressants,24 oral contraceptives,2S and metoclopramide,26 a dopamine antagonist used to treat gastroesophageal reflux. DYSTONIA In dystonia, continual change in muscle tone leads to sustained movements in the face, limbs, or trunk. Generalized dystonia simultaneously involves the axial and appendicular musculature, while focal dystonia is limited to a particular region of the body, such as the face. Dystonia of either variety can induce grotesque facial expressions, and generalized dystonia can also be accompanied by bizarre body postures. The most common form ofgeneralized dystonia is dystonia musculorum deformans, or torsion dystonia. It is an autosomal-dominant genetic disorder, usually of European Jews, that develops in late childhood. Although it eventually causes extraordinarily severe and incapacitating dystonia, torsion dystonia does not cause dementia. Dystonias are also symptoms of juvenile Huntington's disease,9-11 Wilson's disease,27 and other degenerative neurologic conditions, and in each of these illnesses, symptoms appear in late childhood and the dystonia is generalized. Dementia frequently occurs as well. Facial dystonia, a focal dystonia, is typically not accompanied by axial or appendicular dystonia. Common facial dystonias are blepharospasm, Meige's syndrome, tardive dystonia, and hemifacial spasm. These conditions usually develop in middle-aged or older individuals, do not cause dementia, and have no established etiology. Symmetrical, repetitive, prolonged, and forceful contractions (spasms) of the upper and lower muscles of the eyelids (orbicularis oculi) are characteristic of blepherospasm. This condition usually starts with frequent but normal-appearing blinks. As it progresses, patients exhibit longer and more forceful blinks, which are actually dystonic spasms, during which their eyelids become clamped shut. 28 In severe cases, patients are essentially blind because they cannot open 265
Facial Dyskinesias
their eyes. Although blepharospasm might mimic a component of TO, the spasms are longer and buccolingulomasticatory dyskinesia is not seen. Conventional medical and surgical treatments are rarely successful. Clonazepam may reduce the spasms,2 but improvement is limited and lethargy and other, adverse side effects frequently occur. Differential facial-nerve sectioning also reduces the spasms, but patients are often unable to close their eyelids postoperatively, and in many cases the blepharospasm recurs. Intramuscular injections of botulinum A toxin constitute a major advance in the treatment of blepharospasm. Originally developed for use in strabismus,29 this technique has also been useful for treating Meige's syndrome and other dystonic disorders, such as spasmodic torticollis,3O focal appendicular dystoniaJO•31 (e.g., writer's cramp), and spasmodic dysphonia30,32 Botulinum A toxin is the most neurotoxic of eight antigenically different toxins derived from the infamous clostridium botulinum. By binding to the presynaptic neuromuscular junction and preventing the release of acetylcholine, the toxin renders muscles paretic. In 60% to 70% of cases,33-lS botulinum A toxin injected into the orbicularis oculi alleviates blepharospasm for about three months. The injections must be repeated in the majority of patients. 36 Despite the potentially serious nature of complications, side effects have been transient, localized, and mild. 3s--37 If dystonic movements also spread to the lower face, the condition is called Meige's syndrome, a similar but more extensive condition than blepharospasm. Now sometimes known as orofacial dyskinesia, it was previously called Brueghel's syndrome. It consists of dystonic movements of the lower and the upper face. 38 In movements similar to those seen in blepharospasm, the muscle surrounding the mouth, the orbicularis oris, makes grimacing movements and the jaw opens and closed forcefully and slowly. Meige's syndrome has an average age of onset between 40 and 70 years and usually begins as blepharospasm. Some cases are eventually complicated by spastic dysphonia, tremor, and other movement disorders. 2 Meige's syndrome 266
differs from TO in that the movements are symmetrical, slow, sustained, and more extensive, and the tongue is not involved. Medicines that deplete dopamine (tetrabenazine), interfere with central acetylcholine activity (trihexyphenidyl), or alter electrolyte metabolism (lithium) do not alleviate the symptoms of Meige's syndrome. 2.39 In contrast, botulinum A injections provide at least temporary improvement in approximately 40% of cases.33,37 Tardive dystonia is a chronic reaction to dopamine-blocking neuroleptics that can begin up to three months after neuroleptic initiation. It is an iatrogenic condition inducing dystonia of the face that results in various bizarre, usually asymmetrical, contortions. Unlike blepharospasm and Meige's syndrome, tardive dystonia is typically accompanied by appendicular and axial dystonia, particularly of the neck. 2.40.41 The generalized dystonia forces patients into grotesque, disabling postures. In addition, tardive dystonia is often accompanied by other movement disorders associated with neuroleptics, such as buccolingual dyskinesia and akathisia. About 2% of all patients exposed to neuroleptics develop tardive dystonia. 42 Although patients as young as 13 have been affected, the average age of onset is 45.41 Reports of the effectiveness of anticholinergic medications are conflicting,40.42 and it is only recently that dopamine depletors (tetrabenazine and reserpine) have been described as helpfu1.41 Hemifacial spasm (essentially hemifacial dystonia) consists of intermittent but sustained contractions of the muscles on one side of the face, giving the appearance of a prolonged and exaggerated blink of one eye and a smirk of the mouth on the same side of the face. The disorder begins, like Meige's syndrome, with spasms of the orbicularis oculi and spreads to the orbicularis oris and other lower facial muscles, but it is restricted to one side of the face. Hemifacial spasm is disfiguring and obscures vision in the affected eye, but the tongue, neck, trunk, and limbs are not affected. Unlike other facial dyskinesias, hemifacial spasm can be accompanied by facial pain. Pain is typically lancinating and follows the distribution of the trigeminal nerve on the affected side of the face. Also unlike the other PSYCHOSOMATICS
Kaufman
facial dyskinesias, hemifacial spasms persist during sleep, although they decline in the deeper stages:43 Hemifacial spasm is associated with and probably caused by compression of the facial, or seventh cranial, nerve. Compression usually occurs at the point ofexit from the cerebellopontine angle by an aberrant loop of vessel or by a tumor. When facial pain accompanies spasms, it is due to compression ofthe adjacent trigeminal, or fifth cranial, nerve. Removing the compressive lesion requires a craniotomy.44,45 Likewise, decompression of the trigeminal nerve relieves the facial pain. As an alternative to invasive procedures, botulinum A toxin can be injected into the spasmodic muscles. 29 ,35,46 Relieving facial dyskinesias with procedures aimed at the cranial nerves or their neuromuscular junctions, structures outside the central nervous system (CNS), is a new therapeutic strategy. If the total amount of toxin could be held to the same minute quantities used to alleviate blepharospasm and if the toxin could be confined to the face and tongue muscles, botulinum A toxin injections might also prove useful in treating TO.
TREMOR Tremor is rhythmic movement of a body part about a fixed point. Unlike dystonia, tremor is movement in only a single plane. It usually occurs at a frequency ofbetween 2 and 12 Herz (Hz) and does not distort the face or body. Although many conditions induce tremor, several cause a tremor that is virtually restricted to the face or head. In these conditions, the movements are pronounced and disconcerting, but they are distinct from chorea or dystonia. Essential tremor often affects only the head, where it creates a 4- to 8-Hz tremor.47.48 Although the head is prominently involved, the tremor is usually most apparent in the hands, especially when they are extended in fixed positions against gravity. When the larynx is affected, a patient's voice become tremulous. Essential tremor differs from the tremor seen in parkinsonism by the lack of accompanying rigidity or akinesia. It tends to VOLUME 30· NUMBER 3 • SUMMER 1989
develop in patients in their twenties or thirties, and it is a familial disease. Alcoholic beverages transiently suppress essential tremor. Beta-adrenergic blocking agents, such as propranolol, that act outside the CNS are the medications of first choice. The rabbit syndrome is a fine rhythmic shaking of the lips and lower jaw, similar to essential tremor. It is a relatively common condition, especially in institutionalized, elderly, schizophrenic patients. Yassa et al.49 found this disorder in 4.4% of chronic inpatients who were receiving neuroleptics but in none of the patients receiving anticholinergic medications. Because procyclidine, a potent anticholinergic medication, suppresses the tremor,49 rabbit syndrome would be better considered a variety of either parkinsonism or essential tremor than a variation of TO. TICS Tics are stereotyped movements oflightning-like rapidity. Although tics usually involve only facial and neck muscles, they can involve axial, appendicular, and even vocal and respiratory muscles. They can evolve into patterned coordinated sequences.so Vocal tics are usually repetitive nonspecific sounds, such as sniffles. Only a minority of vocal tics manifest coprolalia. 51 The most common motor tics are facial movements, tongue protrusion, and licking.52 The rapid component of motor tics usually moves away from the midline. For example, when a head toss occurs, the head seems to be thrown to the side. Likewise, the mouth movement in a tic generally draws the lateral edge of the lips to the side to form a half-smile rather than toward the midline to form a pucker. Recent investigations have shown that unlike the classic movement disorders, tics persist in sleep.53 Also unlike voluntary movements, tics are not preceded by premovement electroencephalographic potentials that reflect cerebral cortical "anticipation" ofthe movement, 54 suggesting that tics have a subcortical origin. Dopamine-blocking neuroleptics have been the mainstay of treatment for tics associated with Tourette's syndrome. Haloperidol has been the 267
Facial Dyskinesias
drug of choice, and another dopamine-blocking agent, pimozide, has recently been found to be effective.~2 The role of dopamine depletors, such as tetrabenazine, has not been established, and the purported effectiveness of c10nidine has been challenged. ~~~ Some movements associated with motor tics resemble the movements of TO. Both conditions can include respiratory movements and nonspecific vocalizations, and the movements in both can be suppressed with dopamine-blocking neu-
roleptics. Nevertheless, tics are distinct from TO movements in that motor tics are much more rapid than other facial dyskinesias. Tongue movements, a characteristic feature of TO, are rare. Unlike most other facial dyskinesias, tics usually arise in late childhood and wax and wane throughout adult life, and additional tics, including vocal tics, may develop.~1 Already existing tics may also become more complex and repetitive. They are then prone to include structures caudal to the face and head.
References I. Casey DE: Pharmacology of blepharospasm-oromandibular dystonia syndrome. Neurology 30:690-695. 1980 2. Jankovic J. Ford J: Blepharospasm and orofacial-cervical dystonia: clinical and phannacological fmdings in 100 patients. Ann Neuro/13:402-411. 1983 3. Kobayashi RM: Orofacial dyskinesia. West J Med 125:277-288.1976 4. Stahl SM. Yesavage JA. Berger PA: Pharmacologic characteristics of Meige dystonia: differentiation from tardive dyskinesia. J Clin Psychiatry 43:445-446. 1982 5. Cummings JL: Psychosomatic aspects of movement disorders. Adv Psychosom Med 13: 111-132. 1985 6. Burte RE. Fahn S. Jankovic J. et a1: Tardive dystonia: late-onset and persistent dystonia caused by antipsychotic drugs. Neurology 32: 1335-1346. 1982 7. Gardos G. Cole JO. Salomon M. et a1: Clinical forms of severe tardive dyskinesia. Am J Psychiatry 144:895-902. 1987 8. Yassa R. Jones BO: Complications of tardive dyskinesia: a review. Psychosomatics 26:305-313. 1985 9. Bittenbender JB. Quadfasel FA: Rigid and akinetic forms of Huntington's chorea. Arch Neurol7:275-288. 1962 10. Markham CH. Knox JW: Observations on Huntington's chorea in childhood.J Pediatr67:47-57. 1965 II. Shoulson I: Huntington's disease. in Asbury AK. McKhann GM. MacDonald WI (eds): Diseases of the Nervous System. Vol 2. Philadelphia. Saunders. 1986. pp 1258-1267 12. Marlin JB. Gusella JF: Huntington's disease: pathogenesisandmanagement.N EnglJ Med315:1267-1276.1986 13. Nausieda PAt Koller WC. Weiner WJ. et a1: Chorea induced by oral contraceptives. Neurology 29: 16051609.1979 14. Delwaide PJ. Desseilles M: Spontaneous buccolinguofacial dyskinesia in the elderly. Acta Neurol Scand 56:~ 262.1977 15. O·Alessandro R. Benassi G. Cristina E. et a1: 11le prevalence of lingual-facial-buccal dyskinesias in the elderly. Neurology 36:1350-1351. 1986 16. Molsa PK. Marttila RJ. Rinne UK: Extrapyramidal signs 268
in A1zheimer's disease. Neurology 34:1 I 14-1 116. 1984 17. Brandon S. McClelland HA. Protheroe C: A study of facial dyskinesia in a mental hospital population. Br J Psychiatry 118:171-184.1971 18. Weiner WJ. KJawans HL: Lingual-facial-buccal movements in the elderly: I. pathophysiology and treatment. J Am GeriatrSoc21:314-317. 1973 19. Koller WC: Edentulous orodyskinesia. Ann Neurol 13:97-99.1983 20. Suteher HO. Underwood RB. Beatty RA. et a1: Orofacial dyskinesia. lAMA 216: 1459--1463, 1971 21. Kaufman OM: Clinical Neurology for Psychiatrists. Second Ed. Orlando. Aa. Grune & Stratton. 1985. p 333 22. Ichikawa K. Kim RC. Givelber H. et al: Chorea gravidarum. Arch NeuroI37:429--432. 1980 23. Johnson RT. Richardson EP: 11le neurological manifestations of systemic lupus erythematosus: a clinical-pathological study of 24 cases and review of the literature. Medicine 47:337-369. 1968 24. Fann WE. Sullivan JL. Richman BW: Dyskinesias associated with tricyclic antidepressants. Br J Psychiatry 128:490-493.1976 25. Nausieda PAt Koller WC. Weiner WJ. et a1: Chorea induced by oral contraceptives. Neurology 29:16051609.1979 26. Samie MR. Dannenhoffer MA. Rozek S: Case repon: life-threatening tardive dyskinesia caused by metoc1opramide. MovemtntDisordtrs 2: 125-129. 1987 27. Starosta-Rubinstein S. Young AB. KJuin K. et a1: Clinical assessment of 31 patients with Wilson's disease. Arch Neurol44:365-370. 1987 28. Marsden CD: Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). J Neurol Neurosurg Psychiatry 39:1204-1209.1976 29. Scott AB. Kennedy RA. Stubbs HA: Botulinum A toxin injection as a treatment for blepharospasm. Arch OphthalmoI103:347-350. 1985 30. Brio MF. Fahn S. MoskowitzC. et a1: Localized injections of botulinum toxin for the treatment offacial dystonia and hemifacial spasm. Movemtnt Disorders 2:237-254. 1987 PSYCHOSOMATICS
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31. Cohen L, Hallett M, Geller B, et al: Treatment of focal dystonias of the hand with botulinum toxin injection. Neurology 37:123-124,1987 32. Ludlow C, Hallett M, Naunton R, et al: Treatment of spasmodic dysphonia with botulinum toxin injection. Neurology 37: 124, 1987 33. Jankovic J, Onnan J: Botulinum A toxin for cranial cervical dystonia: a double-blind. placebo-controlled study. Neurology 37:616-623, 1987 34. Tsoy EA, Buckley EO, Dutton JJ: Treatment ofblepharospasm with botulinum toxin. Am I Ophtholmol 99: 176179.1985 35. Savino PJ. Sergott RC, Bosley TM. et al: Hemifacial spasm treated with botulinum A toxin injection. Arch Ophtholmol103: 1305-1306, 1985 36. Dutton JJ, Buckley EO: Botulinum toxin in the management of blepharospasm. Arch NeuroI43:380-382, 1986 37. Mauriello JA, Coniaris H: Vse of botulinum in the treatment of 100 patients with blepharospasm. NI Med 84:4344.1987 38. Meige H: Les convulsions de la face: une forme clinique de convulsion faciale: bilaterale et mediane. Rev Neurol (Paris) 2:437-443, 1910 39. Nutt JG. Hammerstad JP. deGarmo P. et al: Cranial dystonia: double-blind crossover study of anticholinergics. Neurology 34:215-217, 1984 40. Burke RE: Tardive dyskinesia: current clinical issues. Neurology 34:1348-1353.1984 41. Hang VJ. Burke RE, Fahn S: Natural history and treatment of tardive dystonia. Movement Disorders 1:193208,1986 42. Yassa R, Nair V, Dimitry R: Prevalence of tardive dystonia. Acta Psychiatr Scand 73:629-633. 1986 43. Montagna P. Imbriaco A, Zucconi M, et al: Hemifacial spasm in sleep. Neurology 36:270-273. 1986 44. Jannetta PJ: Trigeminal neuralgia and hemifacial spasm: etiology and definitive treatment. Arch Neurol 32:353. 1975
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45. Nielsen VK. Jannetta PJ: Pathophysiology of hemifacial spasm: m. effects of facial nerve decompression. Neurology 34:891--897, 1984 46. Carruthers J, Stubbs HA: Botulinum toxin for benign essential blepharospasm. hemifacial spasm, and age-related lower eyelid entropion. Can I Neurol Sci 14:42-45. 1987 47. Martinelli P, Gabellini AS. Gulli MR, et al: Different clinical features of essential tremor: a 200-patient study. Acta Neurol Scand 75: 106-1 II. 1987 48. Findley U. Koller WC: Essential tremor: a review. Neurology37:1 194-1 197. 1987 49. Yassa R. La! S: Prevalence of the rabbit syndrome. Ami Psychiatry 143:656-657, 1986 SO. Jankovic J, Fahn S: The phenomenology of tics. MovementDisorders 1:17-26,1986 51. Shapiro AH. Young JG, Shapiro ES. et al: Gilles de la Tourette's Syndrome, Second Ed. New York. Raven. 1988, pp 127-193 52. Regeur L. Pakkenberg B. Fog R, et al: Clinical features and long-term treatment with pimozide in 65 patients with Gilles de la Tourette's syndrome. I Neurol Neurosurg Psychiatry 49:791-795. 1986 53. Hovacevic R, Ristanovic CC, Goetz CMT. et al: Gilles de la Tourette's syndrome and sleep. Neurology 37:268. 1987 54. Obeso JA, Rothwell JC. Marsden CD: Simple tics in Gilles de la Tourette's syndrome are not prefaced by a normal premovement EEO potential. I Neurol Neurosurg Psychiatry 44:735-738, 1981 55. Goetz CC, Tanner CM. Wilson RS. et al: Clonidine and Gilles de la Tourette's syndrome: double-blind study using objective rating methods. Ann Neurol21 :307-310. 1987 56. Mesularn MM, Petersen RC: Treatment of Gilles de 18 Tourette's syndrome: eight-year, practice-based experience in a predominantly adult population. Neurology 37:1828-1833.1987
269
The face is prominently or exclusively involved in several involuntary movement disorders. called "facial dyskinesias," in addition to the common buccolingualform oftardive dyskinesia. This review describes the appearance ofthe mostfrequently occurring facial dyskinesias: chorea, dystonia. tremor, and tics. Some new treatments are discussed.
nvoluntary movements (dyskinesias) of the face, particularly tardive dyskinesia (TO), are known to be associated with long-tenn neuroleptic use. However, it is less well known that several other neurologic conditions are also characterized by facial dyskinesias. These conditions occur commonly and can be mistaken for a psychogenic disorder or incorrectly assumed to be a manifestation of TO. Some of these other dyskinesias can be associated with dementia and appear at first to be a psychiatric disorder. Because electrophysiologic measurements, e.g., electromyograms, are usually not practical and pharmacologic tests are inconsistent,l-4 facial dyskinesias must be diagnosed almost entirely by their clinical features. In general, they become worse with anxiety and fatigue, are suppressed by concentration, and, with several exceptions, are not present during sleep. While psychiatric disturbances are common in TO and cognitive impainnents are often found in varieties of chorea, most facial dyskinesias are not consistently associated with mental aberrations. s In only a few conditions are there distinctive pathologic changes in the nervous system. Several varieties of facial dyskinesias are discernible; in this review, I will use the common orofacial or buccolingulomasticatory fonn ofTO as the reference point. The important clinical aspects ofTO and other facial dyskinesias are the movement's pattern and rapidity, the area of facial involvement, and the presence ofneck, trunk, and pelvic (axial) or limb (appendicular) involve-
I
VOLUME 30 • NUMBER 3 • SUMMER 1989
ment. By considering these aspects, the clinician can diagnose chorea, dystonia, tremor, and tics (Table I). CHOREA Bodily movements in chorea are rapid, variable, and jerky but relatively simple and nonstereotyped. At times, the movements can appear to be confluent and incessant. Chorea is the predominant dyskinesia of TO and also of choreoathetosis, Huntington's disease, Sydenham's chorea, and senile facial dyskinesia and its varieties. In its early phases and throughout most of its course, TO consists primarily or exclusively of chorea of the tongue, lower face, and jaw. It causes chewing, pouting, sucking, and vennifonn (thrusting) movements of the tongue. 6 It sometimes causes the eyelids to blink severely enough to constitute blepharospasm. 1 TO can be complicated by speech and respiratory disruptions8 similar to those associated with Gilles de la Tourene's syndrome. In advanced cases, the appendicular or axial muscles are affected. Compared to other dyskinesias, TO usually causes linle functional impainnent. Received May 25, 1988; revised August 26, 1988; accepted September 14, 1988. Address reprint requests to Dr. Kaufman, Depanment of Neurology, Montefiore Medical Center, Albert Einstein Col1ege of Medicine, III East 21 Oth Street, Bronx, N.Y., 10467. Copyright © 1989 The Academy of Psychosomatic Medicine.
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TABLE 1. Cbaracteristic:s 01 facial dyskinesia Regions Involved"
Pattemsof Dyskinesia Movement Chorea
Upper Face
nonstereotype
Examples tardive dyskinesiab ++ choreoathetosis ++ Huntington's disease ++
"jerky"
Sydenham'schorea
asymmetric.
Lower Vertical Associated Face Tongue Neck Axis Limbs Dementia ++++
++++
++
++ ++ ++
++ ++ ++
++ ++ ++ ++
++
+++
+++
+
++ +++
+ ++
+++ +++
++++ ++++
++++ ++++
+++
+++
+++
+ ++ ++ ++
+ +++ ++ ++
No No· Yes No
senile/edentulous chorea
Dystonia
Tremor
Tic
generalized or focal, sustained, and predominantly twisting
torsion dystoniac ++ Wilson'sdiseasec +++ d blepharospasm ++++ Meige's syndromed ++++ hemifacial spasmd ++++ tardive dystonia" ++
Yes
++++ ++++f ++
regular, oscillatory at 2 to 12 vibrations per second
essential tremor rabbit syndrome
++++
stereotyped, forceful, irregular, rapid
simple motor tics ++++ Tourene's syndrome ++++
++++ ++++
++
+++ +++
++ ++
No Yes No No No No
++++
No No
++ ++
No No
"Involvement: rare (+); occasional (++); usual (+++); or constant (++++) "Buccolingulomasticatory variety COeneralized variety dt:ocaJ variety "Mental retardation often present fUnilateral involvement
Choreoathetosis is a dyskinesia that consists of chorea superimposed on slow, twisting, and unsustained movements (athetosis). Because choreoathetosis is almost always a congenital disorder resulting from a birth or neonatal injury, such as kernicterus, it is a stable, nonprogressive movement disorder associated with mental retardation, seizures, and spasticity. Although choreoathetosis is typically most prominent in the face, tongue, and neck, where muscles become hypertrophied, it also involves virtually all muscle groups. It often causes terrible functional incapacities, including dysarthria, hand incoordination, and walking difficulties. Unlike the facial dyskinesias of TO, those of choreoathetosis are congenital, continual. writhing, and abrupt. Moreover, they are almost always found in the presence of vocal, axial, and appendicular dyskinesias. 264
Both Huntington's disease and Sydenharn's chorea, two otherwise entirely different disorders, can present with facial chorea. In both conditions, grimacing, tongue protrusion, chewing, puckering, and other facial dyskinesias occur frequently. The facial dyskinesias in these forms of chorea, but not in TO, are almost always accompanied by appendicular and limb chorea, and the voice develops a lilting quality. Huntington's disease also induces dementia that is usually detectable when the chorea appears. A variety of Huntington's disease called "juvenile Huntington's disease" can develop in children. Affected children develop a rigid body posture with an absence of, rather than an excess of, facial movements.9-11 Their appearance mimics naturally occurring or neuroleptic-induced parkinsonism. In a major medical advance, a marker for Huntington's disease has been isolated on chromosome PSYCHOSOMATICS
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4 12; in many cases, the marker has permitted the identification of presymptomatic heterozygote individuals and patients homozygotic for Huntington's disease. Individuals at risk ofdeveloping the disease can also be tested to determine if they are carrying the gene. Sydenham's chorea, a major manifestation of rheumatic fever, affects older children and adolescents. 13 It causes dyskinesias that can mimic tics, hyperactivity, or dyskinesia that develops upon neuroleptic withdrawal. 7 However, it does not cause permanent cognitive or personality changes. Senile facial dyskinesia involves the lower face, jaw, and tongue. Like TO, it produces sucking, lip smacking, and other oral movements that are repetitive but not rhythmic. 14 Reported incidence has ranged from 1.5% in patients older than 66 years lS to 29% in a study of retirement-home patients who were older than 59 years and who had no neurologic complaints.14 The incidence is greater in women and in patients with dementia (38%), but it does not increase with increasing age. 14 Similar dyskinesias have been found in 17% of Alzheimer's disease patients;6 and in schizophrenic patients who had not been exposed to neuroleptics. '7 These movements usually cause .little functional impairment; however, when treatment is necessary, dopamine-blocking neuroleptics reduce or suppress the movements. 14.18 A variation of senile dyskinesia, edentulous dyskinesia or orodyskinesia. occurs in elderly
edentulous individuals. Koller l9 found that 16% of 75 edentulous people had facial dyskinesias, compared with none of the controls. Although this disorder can include an element of dystonia, the movements are essentially indistinguishable from senile facial dyskinesia. 20 Compared with TO, edentulous dyskinesia involves less extensive tongue protrusion and a striking absence of upper-face and other body-area movement. 19 Properly fitting dentures correct this problem. 20 Chorea can be a manifestation of more than a dozen neurologic and general medical conditions,21 including pregnancy22 and systemic lupus erythematosus.23 Types of chorea that mimic TO in both clinical appearance and possible bioVOLUME 30. NUMBER 3· SUMMER 1989
chemical abnormalities can result from many medications besides the well-known antipsychotic preparations. Such medications include tricyclic antidepressants,24 oral contraceptives,2S and metoclopramide,26 a dopamine antagonist used to treat gastroesophageal reflux. DYSTONIA In dystonia, continual change in muscle tone leads to sustained movements in the face, limbs, or trunk. Generalized dystonia simultaneously involves the axial and appendicular musculature, while focal dystonia is limited to a particular region of the body, such as the face. Dystonia of either variety can induce grotesque facial expressions, and generalized dystonia can also be accompanied by bizarre body postures. The most common form ofgeneralized dystonia is dystonia musculorum deformans, or torsion dystonia. It is an autosomal-dominant genetic disorder, usually of European Jews, that develops in late childhood. Although it eventually causes extraordinarily severe and incapacitating dystonia, torsion dystonia does not cause dementia. Dystonias are also symptoms of juvenile Huntington's disease,9-11 Wilson's disease,27 and other degenerative neurologic conditions, and in each of these illnesses, symptoms appear in late childhood and the dystonia is generalized. Dementia frequently occurs as well. Facial dystonia, a focal dystonia, is typically not accompanied by axial or appendicular dystonia. Common facial dystonias are blepharospasm, Meige's syndrome, tardive dystonia, and hemifacial spasm. These conditions usually develop in middle-aged or older individuals, do not cause dementia, and have no established etiology. Symmetrical, repetitive, prolonged, and forceful contractions (spasms) of the upper and lower muscles of the eyelids (orbicularis oculi) are characteristic of blepherospasm. This condition usually starts with frequent but normal-appearing blinks. As it progresses, patients exhibit longer and more forceful blinks, which are actually dystonic spasms, during which their eyelids become clamped shut. 28 In severe cases, patients are essentially blind because they cannot open 265
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their eyes. Although blepharospasm might mimic a component of TO, the spasms are longer and buccolingulomasticatory dyskinesia is not seen. Conventional medical and surgical treatments are rarely successful. Clonazepam may reduce the spasms,2 but improvement is limited and lethargy and other, adverse side effects frequently occur. Differential facial-nerve sectioning also reduces the spasms, but patients are often unable to close their eyelids postoperatively, and in many cases the blepharospasm recurs. Intramuscular injections of botulinum A toxin constitute a major advance in the treatment of blepharospasm. Originally developed for use in strabismus,29 this technique has also been useful for treating Meige's syndrome and other dystonic disorders, such as spasmodic torticollis,3O focal appendicular dystoniaJO•31 (e.g., writer's cramp), and spasmodic dysphonia30,32 Botulinum A toxin is the most neurotoxic of eight antigenically different toxins derived from the infamous clostridium botulinum. By binding to the presynaptic neuromuscular junction and preventing the release of acetylcholine, the toxin renders muscles paretic. In 60% to 70% of cases,33-lS botulinum A toxin injected into the orbicularis oculi alleviates blepharospasm for about three months. The injections must be repeated in the majority of patients. 36 Despite the potentially serious nature of complications, side effects have been transient, localized, and mild. 3s--37 If dystonic movements also spread to the lower face, the condition is called Meige's syndrome, a similar but more extensive condition than blepharospasm. Now sometimes known as orofacial dyskinesia, it was previously called Brueghel's syndrome. It consists of dystonic movements of the lower and the upper face. 38 In movements similar to those seen in blepharospasm, the muscle surrounding the mouth, the orbicularis oris, makes grimacing movements and the jaw opens and closed forcefully and slowly. Meige's syndrome has an average age of onset between 40 and 70 years and usually begins as blepharospasm. Some cases are eventually complicated by spastic dysphonia, tremor, and other movement disorders. 2 Meige's syndrome 266
differs from TO in that the movements are symmetrical, slow, sustained, and more extensive, and the tongue is not involved. Medicines that deplete dopamine (tetrabenazine), interfere with central acetylcholine activity (trihexyphenidyl), or alter electrolyte metabolism (lithium) do not alleviate the symptoms of Meige's syndrome. 2.39 In contrast, botulinum A injections provide at least temporary improvement in approximately 40% of cases.33,37 Tardive dystonia is a chronic reaction to dopamine-blocking neuroleptics that can begin up to three months after neuroleptic initiation. It is an iatrogenic condition inducing dystonia of the face that results in various bizarre, usually asymmetrical, contortions. Unlike blepharospasm and Meige's syndrome, tardive dystonia is typically accompanied by appendicular and axial dystonia, particularly of the neck. 2.40.41 The generalized dystonia forces patients into grotesque, disabling postures. In addition, tardive dystonia is often accompanied by other movement disorders associated with neuroleptics, such as buccolingual dyskinesia and akathisia. About 2% of all patients exposed to neuroleptics develop tardive dystonia. 42 Although patients as young as 13 have been affected, the average age of onset is 45.41 Reports of the effectiveness of anticholinergic medications are conflicting,40.42 and it is only recently that dopamine depletors (tetrabenazine and reserpine) have been described as helpfu1.41 Hemifacial spasm (essentially hemifacial dystonia) consists of intermittent but sustained contractions of the muscles on one side of the face, giving the appearance of a prolonged and exaggerated blink of one eye and a smirk of the mouth on the same side of the face. The disorder begins, like Meige's syndrome, with spasms of the orbicularis oculi and spreads to the orbicularis oris and other lower facial muscles, but it is restricted to one side of the face. Hemifacial spasm is disfiguring and obscures vision in the affected eye, but the tongue, neck, trunk, and limbs are not affected. Unlike other facial dyskinesias, hemifacial spasm can be accompanied by facial pain. Pain is typically lancinating and follows the distribution of the trigeminal nerve on the affected side of the face. Also unlike the other PSYCHOSOMATICS
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facial dyskinesias, hemifacial spasms persist during sleep, although they decline in the deeper stages:43 Hemifacial spasm is associated with and probably caused by compression of the facial, or seventh cranial, nerve. Compression usually occurs at the point ofexit from the cerebellopontine angle by an aberrant loop of vessel or by a tumor. When facial pain accompanies spasms, it is due to compression ofthe adjacent trigeminal, or fifth cranial, nerve. Removing the compressive lesion requires a craniotomy.44,45 Likewise, decompression of the trigeminal nerve relieves the facial pain. As an alternative to invasive procedures, botulinum A toxin can be injected into the spasmodic muscles. 29 ,35,46 Relieving facial dyskinesias with procedures aimed at the cranial nerves or their neuromuscular junctions, structures outside the central nervous system (CNS), is a new therapeutic strategy. If the total amount of toxin could be held to the same minute quantities used to alleviate blepharospasm and if the toxin could be confined to the face and tongue muscles, botulinum A toxin injections might also prove useful in treating TO.
TREMOR Tremor is rhythmic movement of a body part about a fixed point. Unlike dystonia, tremor is movement in only a single plane. It usually occurs at a frequency ofbetween 2 and 12 Herz (Hz) and does not distort the face or body. Although many conditions induce tremor, several cause a tremor that is virtually restricted to the face or head. In these conditions, the movements are pronounced and disconcerting, but they are distinct from chorea or dystonia. Essential tremor often affects only the head, where it creates a 4- to 8-Hz tremor.47.48 Although the head is prominently involved, the tremor is usually most apparent in the hands, especially when they are extended in fixed positions against gravity. When the larynx is affected, a patient's voice become tremulous. Essential tremor differs from the tremor seen in parkinsonism by the lack of accompanying rigidity or akinesia. It tends to VOLUME 30· NUMBER 3 • SUMMER 1989
develop in patients in their twenties or thirties, and it is a familial disease. Alcoholic beverages transiently suppress essential tremor. Beta-adrenergic blocking agents, such as propranolol, that act outside the CNS are the medications of first choice. The rabbit syndrome is a fine rhythmic shaking of the lips and lower jaw, similar to essential tremor. It is a relatively common condition, especially in institutionalized, elderly, schizophrenic patients. Yassa et al.49 found this disorder in 4.4% of chronic inpatients who were receiving neuroleptics but in none of the patients receiving anticholinergic medications. Because procyclidine, a potent anticholinergic medication, suppresses the tremor,49 rabbit syndrome would be better considered a variety of either parkinsonism or essential tremor than a variation of TO. TICS Tics are stereotyped movements oflightning-like rapidity. Although tics usually involve only facial and neck muscles, they can involve axial, appendicular, and even vocal and respiratory muscles. They can evolve into patterned coordinated sequences.so Vocal tics are usually repetitive nonspecific sounds, such as sniffles. Only a minority of vocal tics manifest coprolalia. 51 The most common motor tics are facial movements, tongue protrusion, and licking.52 The rapid component of motor tics usually moves away from the midline. For example, when a head toss occurs, the head seems to be thrown to the side. Likewise, the mouth movement in a tic generally draws the lateral edge of the lips to the side to form a half-smile rather than toward the midline to form a pucker. Recent investigations have shown that unlike the classic movement disorders, tics persist in sleep.53 Also unlike voluntary movements, tics are not preceded by premovement electroencephalographic potentials that reflect cerebral cortical "anticipation" ofthe movement, 54 suggesting that tics have a subcortical origin. Dopamine-blocking neuroleptics have been the mainstay of treatment for tics associated with Tourette's syndrome. Haloperidol has been the 267
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drug of choice, and another dopamine-blocking agent, pimozide, has recently been found to be effective.~2 The role of dopamine depletors, such as tetrabenazine, has not been established, and the purported effectiveness of c10nidine has been challenged. ~~~ Some movements associated with motor tics resemble the movements of TO. Both conditions can include respiratory movements and nonspecific vocalizations, and the movements in both can be suppressed with dopamine-blocking neu-
roleptics. Nevertheless, tics are distinct from TO movements in that motor tics are much more rapid than other facial dyskinesias. Tongue movements, a characteristic feature of TO, are rare. Unlike most other facial dyskinesias, tics usually arise in late childhood and wax and wane throughout adult life, and additional tics, including vocal tics, may develop.~1 Already existing tics may also become more complex and repetitive. They are then prone to include structures caudal to the face and head.
References I. Casey DE: Pharmacology of blepharospasm-oromandibular dystonia syndrome. Neurology 30:690-695. 1980 2. Jankovic J. Ford J: Blepharospasm and orofacial-cervical dystonia: clinical and phannacological fmdings in 100 patients. Ann Neuro/13:402-411. 1983 3. Kobayashi RM: Orofacial dyskinesia. West J Med 125:277-288.1976 4. Stahl SM. Yesavage JA. Berger PA: Pharmacologic characteristics of Meige dystonia: differentiation from tardive dyskinesia. J Clin Psychiatry 43:445-446. 1982 5. Cummings JL: Psychosomatic aspects of movement disorders. Adv Psychosom Med 13: 111-132. 1985 6. Burte RE. Fahn S. Jankovic J. et a1: Tardive dystonia: late-onset and persistent dystonia caused by antipsychotic drugs. Neurology 32: 1335-1346. 1982 7. Gardos G. Cole JO. Salomon M. et a1: Clinical forms of severe tardive dyskinesia. Am J Psychiatry 144:895-902. 1987 8. Yassa R. Jones BO: Complications of tardive dyskinesia: a review. Psychosomatics 26:305-313. 1985 9. Bittenbender JB. Quadfasel FA: Rigid and akinetic forms of Huntington's chorea. Arch Neurol7:275-288. 1962 10. Markham CH. Knox JW: Observations on Huntington's chorea in childhood.J Pediatr67:47-57. 1965 II. Shoulson I: Huntington's disease. in Asbury AK. McKhann GM. MacDonald WI (eds): Diseases of the Nervous System. Vol 2. Philadelphia. Saunders. 1986. pp 1258-1267 12. Marlin JB. Gusella JF: Huntington's disease: pathogenesisandmanagement.N EnglJ Med315:1267-1276.1986 13. Nausieda PAt Koller WC. Weiner WJ. et a1: Chorea induced by oral contraceptives. Neurology 29: 16051609.1979 14. Delwaide PJ. Desseilles M: Spontaneous buccolinguofacial dyskinesia in the elderly. Acta Neurol Scand 56:~ 262.1977 15. O·Alessandro R. Benassi G. Cristina E. et a1: 11le prevalence of lingual-facial-buccal dyskinesias in the elderly. Neurology 36:1350-1351. 1986 16. Molsa PK. Marttila RJ. Rinne UK: Extrapyramidal signs 268
in A1zheimer's disease. Neurology 34:1 I 14-1 116. 1984 17. Brandon S. McClelland HA. Protheroe C: A study of facial dyskinesia in a mental hospital population. Br J Psychiatry 118:171-184.1971 18. Weiner WJ. KJawans HL: Lingual-facial-buccal movements in the elderly: I. pathophysiology and treatment. J Am GeriatrSoc21:314-317. 1973 19. Koller WC: Edentulous orodyskinesia. Ann Neurol 13:97-99.1983 20. Suteher HO. Underwood RB. Beatty RA. et a1: Orofacial dyskinesia. lAMA 216: 1459--1463, 1971 21. Kaufman OM: Clinical Neurology for Psychiatrists. Second Ed. Orlando. Aa. Grune & Stratton. 1985. p 333 22. Ichikawa K. Kim RC. Givelber H. et al: Chorea gravidarum. Arch NeuroI37:429--432. 1980 23. Johnson RT. Richardson EP: 11le neurological manifestations of systemic lupus erythematosus: a clinical-pathological study of 24 cases and review of the literature. Medicine 47:337-369. 1968 24. Fann WE. Sullivan JL. Richman BW: Dyskinesias associated with tricyclic antidepressants. Br J Psychiatry 128:490-493.1976 25. Nausieda PAt Koller WC. Weiner WJ. et a1: Chorea induced by oral contraceptives. Neurology 29:16051609.1979 26. Samie MR. Dannenhoffer MA. Rozek S: Case repon: life-threatening tardive dyskinesia caused by metoc1opramide. MovemtntDisordtrs 2: 125-129. 1987 27. Starosta-Rubinstein S. Young AB. KJuin K. et a1: Clinical assessment of 31 patients with Wilson's disease. Arch Neurol44:365-370. 1987 28. Marsden CD: Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). J Neurol Neurosurg Psychiatry 39:1204-1209.1976 29. Scott AB. Kennedy RA. Stubbs HA: Botulinum A toxin injection as a treatment for blepharospasm. Arch OphthalmoI103:347-350. 1985 30. Brio MF. Fahn S. MoskowitzC. et a1: Localized injections of botulinum toxin for the treatment offacial dystonia and hemifacial spasm. Movemtnt Disorders 2:237-254. 1987 PSYCHOSOMATICS
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31. Cohen L, Hallett M, Geller B, et al: Treatment of focal dystonias of the hand with botulinum toxin injection. Neurology 37:123-124,1987 32. Ludlow C, Hallett M, Naunton R, et al: Treatment of spasmodic dysphonia with botulinum toxin injection. Neurology 37: 124, 1987 33. Jankovic J, Onnan J: Botulinum A toxin for cranial cervical dystonia: a double-blind. placebo-controlled study. Neurology 37:616-623, 1987 34. Tsoy EA, Buckley EO, Dutton JJ: Treatment ofblepharospasm with botulinum toxin. Am I Ophtholmol 99: 176179.1985 35. Savino PJ. Sergott RC, Bosley TM. et al: Hemifacial spasm treated with botulinum A toxin injection. Arch Ophtholmol103: 1305-1306, 1985 36. Dutton JJ, Buckley EO: Botulinum toxin in the management of blepharospasm. Arch NeuroI43:380-382, 1986 37. Mauriello JA, Coniaris H: Vse of botulinum in the treatment of 100 patients with blepharospasm. NI Med 84:4344.1987 38. Meige H: Les convulsions de la face: une forme clinique de convulsion faciale: bilaterale et mediane. Rev Neurol (Paris) 2:437-443, 1910 39. Nutt JG. Hammerstad JP. deGarmo P. et al: Cranial dystonia: double-blind crossover study of anticholinergics. Neurology 34:215-217, 1984 40. Burke RE: Tardive dyskinesia: current clinical issues. Neurology 34:1348-1353.1984 41. Hang VJ. Burke RE, Fahn S: Natural history and treatment of tardive dystonia. Movement Disorders 1:193208,1986 42. Yassa R, Nair V, Dimitry R: Prevalence of tardive dystonia. Acta Psychiatr Scand 73:629-633. 1986 43. Montagna P. Imbriaco A, Zucconi M, et al: Hemifacial spasm in sleep. Neurology 36:270-273. 1986 44. Jannetta PJ: Trigeminal neuralgia and hemifacial spasm: etiology and definitive treatment. Arch Neurol 32:353. 1975
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45. Nielsen VK. Jannetta PJ: Pathophysiology of hemifacial spasm: m. effects of facial nerve decompression. Neurology 34:891--897, 1984 46. Carruthers J, Stubbs HA: Botulinum toxin for benign essential blepharospasm. hemifacial spasm, and age-related lower eyelid entropion. Can I Neurol Sci 14:42-45. 1987 47. Martinelli P, Gabellini AS. Gulli MR, et al: Different clinical features of essential tremor: a 200-patient study. Acta Neurol Scand 75: 106-1 II. 1987 48. Findley U. Koller WC: Essential tremor: a review. Neurology37:1 194-1 197. 1987 49. Yassa R. La! S: Prevalence of the rabbit syndrome. Ami Psychiatry 143:656-657, 1986 SO. Jankovic J, Fahn S: The phenomenology of tics. MovementDisorders 1:17-26,1986 51. Shapiro AH. Young JG, Shapiro ES. et al: Gilles de la Tourette's Syndrome, Second Ed. New York. Raven. 1988, pp 127-193 52. Regeur L. Pakkenberg B. Fog R, et al: Clinical features and long-term treatment with pimozide in 65 patients with Gilles de la Tourette's syndrome. I Neurol Neurosurg Psychiatry 49:791-795. 1986 53. Hovacevic R, Ristanovic CC, Goetz CMT. et al: Gilles de la Tourette's syndrome and sleep. Neurology 37:268. 1987 54. Obeso JA, Rothwell JC. Marsden CD: Simple tics in Gilles de la Tourette's syndrome are not prefaced by a normal premovement EEO potential. I Neurol Neurosurg Psychiatry 44:735-738, 1981 55. Goetz CC, Tanner CM. Wilson RS. et al: Clonidine and Gilles de la Tourette's syndrome: double-blind study using objective rating methods. Ann Neurol21 :307-310. 1987 56. Mesularn MM, Petersen RC: Treatment of Gilles de 18 Tourette's syndrome: eight-year, practice-based experience in a predominantly adult population. Neurology 37:1828-1833.1987
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