Movement Disorders Vol. 6, No. 3, 1991, pp. 230-236 0 1991 Movement Disorder Society
Tremor and Idiopathic Dystonia C. P. Jedynak, *A. M. Bonnet and "Y. Agid Centre Medico-Chirurgical Foch, Suresnes, and *Clinique de Neurologie et de Neuropsychologie and INSERM U.289, Hdpital de la SalpCtriere, Paris, France
Summary: The clinical and electromyographic characteristics of tremor were studied in 45 patients presenting with various forms of idiopathic dystonia. Dystonic tremor was shown to be postural, localized, and irregular in amplitude and periodicity, absent during muscle relaxation, exacerbated by smooth muscle contraction, and associated frequently with myoclonus. Although it resembles essential tremor, dystonic tremor seems to be a distinct entity: it is more irregular with a broader range of frequencies; it is asymmetric and remains localized; myoclonus is sometimes associated. This type of tremor is most often seen in the presence of dystonia, but may be observed without evident dystonic symptoms. Key Words: Tremor-Idiopathic dystonia.
The initial description of dystonia musculorum deformans by Oppenheim (1) associated tremor with the dystonic symptom. A high proportion of tremor was observed among patients with the familial form of the disease examined by Larsson and Sjogren (2). In all the patients that Yanagisawa examined by electromyography (EMG), dystonia was associated with rhythmic activity (3). In a study of generalized nonfamilial idiopathic dystonia, 14% of the patients presented with tremor (4). Tremor has also been observed in focal forms of the disease ( 5 ) . Among 132 patients with spasmodic torticollis studied by EMG (6), rhythmic activity was observed in 40% of the cases and tremor of the upper limbs in 21%. Tremor of the hand used for writing has been reported in almost half of the subjects with writer's cramp that have been studied (7,8). Thus, tremor, most often qualified as essential tremor, accompanies dystonia, whether it be generalized, segmental or focal, sporadic or hereditary. Conversely, the presence of focal dystonia is regularly observed in studies of essential tremor. Spasmodic torticollis accompanies essential tremor in about 10% of cases (9,lO); a figure of 3% was re-
ported in the Rochester epidemiological study (11). Writing tremor may be categorized somewhere between idiopathic dystonia and essential tremor (12). According to Rothwell et al. (13), it has a character of its own and differs from benign essential tremor, which is devoid of dystonic elements. In the present study, we have determined the clinical and electromyographic characteristics of tremor observed in generalized, segmental, and focal forms of idiopathic dystonia.
PATIENTS Forty-five patients were studied between 1977 and 1987, 32 in the electrophysiology laboratory of the SalpCtribre Hospital (Paris) and 13 at the C.M.C. Foch (Suresnes, France). Dystonia was diagnosed by clinical observation and EMG. Despite clinical similarities with idiopathic forms of the disease, secondary dystonias were excluded. Patients presenting with various forms of idiopathic dystonia who complained of tremor were included in the study, and were divided into two groups according to the type of tremor and the territory affected. A third group of patients, included for comparison, had tremor with electromyographic features similar to those of the other patients, but no observable dystonic symptoms.
Address correspondence and reprint requests to Dr. P. Jedynak, CMC Foch, 92150 Suresnes, France.
230
TREMOR AND IDIOPATHIC D YSTONIA
Group I Generalized and Segmental Dystonias
231
cases, where the tremor or dystonia affected more than the selective hand and function, were of early onset. None of the patients in this group reported affected family members.
Group I was composed of 10 patients (Table 1). Dystonia was generalized in three cases, and affected the face, neck, upper members, and trunk in four other cases, sparing the pelvis and lower limbs. A single limb was affected in three patients. In one case, dystonia was limited to one lower limb. Two patients had familial dystonia, and three patients mentioned tremor in near relatives.
Group 111: Focal Tremor without Concomitant Symptomatic Dystonia This group was composed of eight patients (Table 3), five of whom had selective writing tremor, and three of whom had tremor of the neck. No tremor of the upper limbs or the voice was observed. The sister of one of the patients also had cervical tremor, and another patient came from a family with a history of focal dystonias including blepharospasm and a case of spasmodic torticollis.
Group 11: Focal Dystonias Twenty-one patients presented a clinical picture in which spasmodic torticollis predominated (Table 2). In seven cases, cervical dystonia also encompassed the scapular muscles. In three cases, dystonia also affected the upper members, but to a lesser degree. In 10 of the 21 patients, the tremor affected one or both upper limbs. In one case (no. l l ) , spasmodic torticollis was associated with writing tremor, without dystonia of the hand. Four patients described contraction of the hand while writing, and four reported tremor in a parent. Eight other patients who had predominant focal dystonia of the hand (Table 2) complained mainly of functional tremor: in the right hand when playing the piano in one case, and while writing in the others. The dystonic cramps and tremor were associated with difficulty in executing fine movements in one patient, dystonic posture of the whole upper limb while walking in another, and postural tremor of the fingers and the hand in two others. These
METHOD For each patient, in addition to the anamnesis and clinical examination, EMG activity was recorded with surface electrodes placed on the muscles involved in the abnormal movement. Activity from a minimum of two pairs of muscles was recorded, except for the functional dystonias, where at least one agonist-antagonist pair was studied. Tremor was evidenced on the EMG and on the accelerometer trace. The protocol included study of (a) spontaneous activity at rest; (b) factors that modify the intensity of the activity (mental calculation, voluntary movement of another segment of the body, antagonistic movement); (c) maintenance of imposed
TABLE 1. Tremor in patients with generalized and segmental dystonias Age (yr)
Onset age (yr)
Patient
Sex
1 2 3 4
F F F M
33 20 62 31
17 15 59 12
5
M
29
6
6 I
M F
30 16
15
8 9 10
F F F
59 16 34
49
14 15
30
Dystonia
Tremor
Site
Intensity"
Siteb
Intensity"
Frequency (Hz)
Myoclonus
Gen. Gen . Gen. Right arm, face, neck Arms, face, neck, larynx Arms, neck Right arm, neck Right arm Left leg Right arm
++++
Right arm Right arm Left arm Right arm
+ ++ ++ +++ ++ + ++ ++ +++ +++
> 12
-
++++ ++ ++ ++
Right arm
+++ ++
Right arm Right arm
++
Right arm Left leg Right arm
+ +
5 9-10
+ -
6
-
4
-
8
-
-d 5-9 5.5 10
+ + -
-
Gen., generalized. a Scored + to + + + (see ref. 15). Site of electromyogram recording. +, 1 g. Nonperiodic; frequency indeterminable.
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C . P.JEDYNAK ET AL.
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TABLE 2. Tremor in patients with .focal dystonias
Patient
Age (yr)
Sex
Neck-predominant 11 F 12 F 13 M
Dystonia
Onset age (yr)
tremor 23 30 42
6 29 38
Site
Intensity
Site
+++ ++ +++ ++ + + + ++ ++ ++ ++ ++ ++ + +++
Right armc Right arm Neck
14
F
35
35
15
M
31
30
16 17 18 19 20 21 22 23 24 25 26 27
M F F M M M
F
35 32 35 25 67 65 30 69 42 52 29 38
15 31 25 21 66 58 9 59 37 49 24 20
Neck Neck, scap Neck, scap, right arm Neck, scap, arms Neck, scap, left arm Neck Neck Neck, scap Neck, scap Neck Neck Neck Neck Neck Neck Neck Neck
28 29
M F
46 51
45 48
Neck Neck
30 31
F
67
64
M
44
42
Neck Neck
F F F F M
Patient
Sex
Age (yr)
Tremor
++ ++ +++ ++ ++ +++
Neck Neck Right arm Neck Arms Neck Neck Neck,d right arm Right,d left arms Neck, left armd Neck Neck Neck, right armd Neck, right,d left arms Neckd Right, leftd arms, legs Neck Neck, right,d left arms
20
33 34
M M
68 25
63 10
35
M
34
8
36
F
63
54
37 38 39
M F M
23 43 52
10 30 52
Frequency (Hz)
+ ++ ++ + + +++ ++ ++ + ++ ++ ++ ++ +++ + ++ +++ + ++ + +
6 10 10 >10
I 8 5 > 12 7 6 5 5 -e 8 5
> 12 10 10 10
Tremor
Onset age (yr)
Hand-predominant tremor 32 M 20
Intensity
Writer’s cramp, fine movements Instrumental cramp (piano) Writer’s cramp, dystonia (right arm) Writer’s cramp, postural tremor (right arm) Writer’s cramp, postural tremor (arms) Writer’s cramp Writer’s cramp Writer’s cramp
Intensity
Frequency (Hz)
Myoclonus
++ + + + ++ ++ ++ ++
5
-
6 10
+
6
-
7
-
4.5 8-12
+ +
-d
-
scap, scapular arch. Scored + to + + + (see ref. 15). b + , 1 g. Writing tremor. Site of electromyogram recording. Nonperiodic; frequency indeterminable. a
++
postures; and (d) voluntary movement and passive movement imposed by the examiner. The shortening reaction (14) was elicited. Muscular activity was recorded with an electroencephalograph. The intento sity of dystonic activity was scored from + + (15). The intensity of tremor was measured by the accelerometer and scored + , , or
+
+
Movement Disorders, Vol. 6 , No. 3, 1991
+ ++
+++
, according to whether acceleration was I g. Myoclonus was defined as abrupt muscular contractions, isolated in a given limb or synchronously involving an agonistantagonist couple, that are repeated with no definite period or with a frequency S3 Hz, in which case it no longer has the appearance of tremor.
TREMOR AND IDIOPATHIC DYSTONIA
233
TABLE 3. Focal tremor without concomitant symptomatic dystonia
Patient
Sex
Age (yr)
40 41 42 43 44 45 46 47
F M M M M F F F
55 63 20 43 52 68 64 62
a
Tremor
Onset age (yr)
Site
Intensitya
54 60 20 ? 51 61 46 55
Writer’s tremor Writer’s tremor Writer’s tremor Writer’s tremor Writer’s tremor Head tremor Head tremofl Head tremorC
+ ++ ++ ++ ++ +++ + ++
Frequency (Hz)
Myoclonus
6-7 7 7 7
-d 4-6 4.5 4.5
+, 1 g. A sister also had head tremor. Familial focal dystonia. Nonperiodic; frequency indeterminable.
RESULTS The results for the three groups of patients are presented in Tables 1-3. Involuntary muscular activity has been analyzed according to the type of movement (tremor, myoclonus, or dystonia) and the circumstances in which it appears. Types of Abnormal Movements Tremor Tremor was observed in all patients. Most often it was The amp1itude and duration Of each burst of contraction were variable and differed from preceding Or succeeding bursts. In agonistantagonist COUPh repetitive bursts did not alternate, but seemed rather to be imperfectly sYnchronized. The mean frequency of the tremor in a given segment (neck or arm) was constant in a given patient, but could vary among segments (e.g., patient 15). The frequency varied among patients from 4 to 12 Hz, and was often situated between 6 and 8 Hz. At neck level, slower or faster frequencies were observed. Above 10 Hz, rhythmic activity of what ap-
peared to be continuous muscle contractions could be detected only by EMG. In general, these tremors could be stopped by strong voluntary or involuntary contractions of the affected muscles. For example, in a form of spasmodic torticollis with tremor, the tremor-inducing activity was attenuated or disappeared when the head of the patient was involuntarily or forcibly turned, but reappeared or increased when the head was held straight (Fig. 1). Tremor was strictly localized. In the neck, it affected the rotator but spared the phonator muscles. voice tremor never occurred in spasmodic torticollis of the tremor type. Tremor of the upper limbs often spared the neck, and always spared the lower limbs and voice. The tremor that accompanied writer’s cramp was always located in the hand used for writing, sparing the root of the limb and contralateral upper limb. MYoclonus Myoclonus was observed in 14 patients distributed among the three groups. The bursts of contraction were highly variable, but always lasted >80 ms
R Splenius c .
FIG. 1. In this patient with right-oriented spasmodic torticollis (case 24), the tremor, which occurs preferentially in the left sternomastoid muscle where dystonia is predominant, appears when the head is intentionally held straight.
Sternornast. Sternornast.
L Splenius c.
Turned to the Right.
Straight.
to the left
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C.P . JEDYNAK ET AL.
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(250 on the average). Both tremor and myoclonus could occur together in the same muscle whether in the neck (Fig. 2) or in the limbs. Dystonia Continuous or discontinuous involuntary muscle contractions were present in all the patients of groups I and 11. When continuous, the contractions were reinforced by spontaneous or provoked spasms lasting several seconds. Discontinuous contractions consisted of spasmodic bursts lasting from a half to several seconds, separated by periods of silence. The interplay between agonist and antagonist muscles was disturbed. Voluntary contractions of agonist muscles were abnormally large in amplitude, and antagonist activity persisted instead of being inhibited. The shortening reaction was elicited by passive movement. Appearance of Abnormal Movements When upper limbs were affected, tremor or myoclonus usually appeared during muscle contraction, regardless of whether it involved a movement, maintenance of a position, or a gesture. It should be noted that in the latter case, the abnormal movement was reinforced both when the gesture was initiated and when it approached its goal. Intention played only a moderate role. When myoclonic activity was ample, it could be observed at rest, and was facilitated by emotion or the presence of the examiner. Tremor and myoclonus affecting the cervical muscles could be observed in the patients while seated, in the absence of any activity. Rotation of the neck, either voluntary or caused by a dystonic
spasm, generally eliminated the tremor or the myoclonus. Among focal dystonias, writing or playing a musical instrument triggered the dystonia, tremor, or myoclonus, either immediately or after a few seconds. DISCUSSION In some patients, tremor was present in the territory of the dystonic symptom. This was the case, for example, when spasmodic torticollis was accompanied by tremor of the head, or when writer's cramp was associated with tremor of the hand. In other cases, when spasmodic torticollis was associated with writing tremor or tremor of the hands, the focal dystonia and the tremor were distant from each other. The third group of patients had no dystonic symptoms. In all the cases studied, however, the characteristics of the tremor, which we purposefully call dystonic, were similar with respect to location, frequency, periodicity and the circumstances in which it appeared. The main characteristics of dystonic tremor are as follows. (a) It is a postural tremor, frequently associated with myoclonus. (b) It is localized and irregular in amplitude and periodicity. (c) It disappears when the muscle is relaxed. (d) It appears with muscle contractions needed to maintain a position or perform movements not requiring intense muscular effort. It is a postural tremor. These observations raise several questions concerning the relation between dystonic tremor and myoclonic dystonia, the respective roles of dystonic and essential tremor in postural tremor, and the existence of isolated dystonic-like tremor in the absence of dystonic symptoms.
l&secToop 1
R
Splenius c.
R
Sternomast.
L Sternomast.
L
Splenius c.
Accel. l g [
Movement Disorders, Vol. 6 , No. 3, 1991
FIG. 2. Myoclonus in the same muscle where tremor was recorded a few seconds earlier (case 21).
TREMOR AND IDIOPATHIC D YSTONIA Dystonic Tremor and Myoclonus The notion that tremor often accompanies idiopathic dystonia is uncontested, even if the prevalence of the association is controversial. High figures, on the order of 80%, were advanced by Larsson and Sjogren (2) for generalized dystonia, and by Couch et al. ( 5 ) for spasmodic torticollis. Figures in the range of 15% (1) to 40% (6) are more common. This tremor, considered to be authentic, is often termed essential tremor. The two groups of dystonic patients studied all complained of tremor (the criterion of inclusion) that was confirmed clinically and recorded by EMG. However, some features of this tremor, irregular period and partially synchronized bursts of synergistic muscles, resemble myoclonus. Myoclonic dystonias have also been reported by Obeso et al. (16). Is there a difference between dystonic tremor and myoclonic dystonia? In the former, the activity is rhythmic and appears when a posture is assumed. In the latter, the bursts of muscular activity can be recorded even at rest, although they are facilitated by postures and movements, and recur at irregular intervals. Intermediate forms exist, however. In the group of patients studied by Obeso et al. (16), the myoclonus was rhythmic in one case. In our series, myoclonus was present in addition to tremor in a third of the patients. Tremor and myoclonus could appear successively in the same muscle during the same examination. However, certain dystonic tremors are borderline cases, where the distinction between tremor and myoclonus is difficult to establish. Dystonic Tremor and Essential Tremor A progressive shift in meaning has led to the inclusion of various postural tremors under the term essential tremor. Marsden et al. (17) distinguish several forms of essential tremor: exaggerated physiological tremor, benign and severe essential tremor, symptomatic tremor in peripheral neuropathies, and tremor in dystonia. The heterogeneity of these tremors has been the subject of debate (18). Another classification of postural tremors is possible, restricting the definition of essential tremor. In this case, essential tremor is considered as a disease characterized by isolated tremor, in the absence of any other neurological manifestation (19). In general, tremor is localized at the extremity of the two upper limbs (9), sometimes affecting the neck and the voice. Isolated voice tremor (20), like orthostatic tremor (21), seems to be a clinical vari-
235
ant of the same disease. Absent at rest, tremor of the upper members appears when positions are assumed or during the performance of fine movements like writing. Its frequency reaches a maximum of 6-8 Hz, and is slower on the side where the amplitude of the tremor is greatest (22). The tremor progresses slowly but inexorably, like degenerative diseases. With age, the territory of the tremor becomes more extended, its amplitude increases, and its frequency slows. When severe, it can impede or render impossible the elementary activities of daily life (23). The tremor that accompanies idiopathic dystonia resembles essential tremor because of its postural character, but is distinguished by its clinical and EMG features. The range of frequencies is broader and the tremor more irregular. Myoclonus, never seen in essential tremor, is sometimes present. The site of the tremor and its evolution are different. More localized and less symmetric, dystonic tremor, once established, remains stable as to its site, amplitude, and frequency. Although this type of tremor is usually observed in the presence of dystonia, it may also occur alone, without evident dystonic symptoms (Table 3). In the absence of radiological, biological, or anatomopathological criteria, the distinction between essential and dystonic tremor can be made on genetic grounds. Starting from the initial study of Velander et al. (24), Larsson and Sjogren studied the familial character of essential tremor (19) and dystonia musculorum deformans (2), including a number of forms with tremor. They concluded that there was no relationship between the two diseases. Dystonic Tremor without Dystonic Symptoms In an extensive family of dystonic subjects, Yanigasawa et al. (25) showed that expression of the abnormal gene was sometimes limited to an isolated tremor with no other dystonic symptoms. Because sporadic idiopathic dystonia cannot be distinguished from the hereditary form on the basis of clinical criteria, it is conceivable that other cases of isolated tremor may also be the consequence of dystonic disease. This hypothesis is supported by the similarities observed between tremor in dystonic patients (Tables 1 and 2) and the writing tremor or tremor of the head observed in the absence of dystonic symptoms (Table 3): irregular frequency and period, associated myoclonus , segmental localization, and clinical stability. According to this hypothesis, then, certain writing tremors would
Movement Disorders, Vol. 6 . N o . 3, 1991
C . P . JEDYNAK ET AL.
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be pure forms of writer’s cramp without the dystonic symptom. This was the case with one of our patients with cervical dystonia who had writing tremor but no dystonia of the hand. The efficacy of anticholinergic medication in the treatment of both dystonia (26,27) and writing tremor (28) that resembles myoclonic dystonia (29) also supports this assumption. A case of writing tremor has been reported in a family with focal dystonia (30). A third source of support for the hypothesis is the observation that cervical and truncal tremor sometimes precedes the onset of spasmodic torticollis by several years (31). According to Baxter et al. (lo), the prognosis of certain cervical tremors is compromised by the risk that true spasmodic torticollis will develop. If our hypothesis is correct, this tremor should be considered as an initial manifestation of dystonia. One of our patients with cervical tremor indeed came from a family with focal dystonias. The gene responsible for idiopathic familial dystonia has recently been localized (32), and the genetics of hereditary forms of essential tremor are under study. These studies should show that the tremor observed in idiopathic dystonia is not associated essential tremor, but a form of tremor with its own clinical and EMG features. Tremors with the same characteristics, observed in the absence of symptomatic dystonia, may be due to dystonic disease. REFERENCES 1 . Oppenheim H. Uber eine eigenartige Krampfkrankheit des kindlichen und jungendichen Alters (dysbasia lordotica progressiva, dystonia musculorum deformans). Neuro Cbl 191 1 ;30:1090-107. 2. Larsson T, Sjogren T. Dystonia musculorum deformans. A genetic and clinical population study of 121 cases. Acta Neurol Scand 1966;42(suppl 17):1-233. 3. Yanagisawa N, Goto A. Dystonia musculorum deformans. Analysis with electromyography. J Neurof Sci iY71;13:3965. 4. Marsden CD, Harrison MJG. Idiopathic torsion dystonia (dystonia musculorum deformans). A review of forty-two patients. Brain 1974;97:793-810. 5. Couch JR. Dystonia and tremor in spasmodic torticollis. In: Eldridge R, Fahn S, eds. Advances in neurology. Vol. 14: Dystonia. New York: Raven Press, 1976:245-58. 6. Rondot P, Jedynak CP, Ferrey G, eds. Le torticolis spasmodique. Rapport de neurologie. In: CongrPs de psychiatrie et de neurologie de langue francaise. Paris: Masson, 1981:l57. 7. Rondot P, Jedynak CP. Dystonies de fonction. Neurologie 1976;9:17007 C20. 8. Sheehy MP, Marsden CD. Writer’s cramp. A focal dystonia. Brain 1982;105:461-80.
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9. Critchley E. Clinical manifestations of essential tremor. J Neurol Neurosurg Psychiatr 1972;35:365-72. 10. Baxter DW, La1 S. Essential tremor and dystonic syndromes. In: Poirier LJ, Sourkes TL, BBdard PJ, eds. Advances in neurology. Vol. 24: The extrapyramidal system and its disorders. New York: Raven Press, 1979:373-7. 1 1 . Rajput AH, Offord KP, Beard CM, Kurland LT. Essential tremor in Rochester, Minnesota: a 45-year study. J Neurol Neurosurg Psychiatr 1984;47:466-70. 12. Rosenbaum F, Jankovic J. Focal task specific tremor and dystonia. Neurology 1988;38:522-7. 13. Rothwell JC, Traub MM, Marsden CD. Primary writing tremor. J Neurol Neurosurg Psychiatr 1979;42:1106-14. 14. Rondot P, Scherrer J. Contraction rBflexe provoqute par le raccourcissement passif du muscle dam l’athttose et les dystonie d’attitude. Rev Neurol 1966;114:329-336. 15. Burke RE, Fahn S, Marsden CD, Bressman SB, Moscowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 1985;35:73-77. 16. Obeso JA, Rothwell JC, Lang AE, Marsden CD. Myoclonic dystonia. Neurology 1983;33:825-830. 17. Marsden CD, Obeso J, Rothwell JC. Benign essential tremor is not a single entity. In: Yahr MD, ed. Current concepts in Parkinson’s disease. Amsterdam: Excerpta Medica, 1983: 3146. 18. Elbe RJ. Physiologic and essential tremor. Neurology 1986; 36:225-231. 19. Larsson T, Sjogren T. Essential tremor. A clinical and genetic population study. Acta Psychiatr Neurol Scand 1960; 3 6 ( ~ ~ p 144): p l 1-1 76. 20. Hatchinsky VC. The nature of primary vocal tremor. Can J Neurol Sci 1975;2:195-197. 21. Heilrnan KM. Orthostatic tremor. Arch NeurollY84;41:880881. 22. Homberg V, Hefter H, Reiners K, Freund HJ. Differential effects of changes in mechanical limb properties on physiological and pathological tremor. J Neuiol Neurosurg Psychiatr 1987;50:568-79. 23. Koller WC, Biaryn, Rubino FA. Essential tremor variants. Neurology 1986;36(suppl 1):121-2. 24. Velander F. Arftlighetestudier inom trenne slakter med hereditar tremor. Nord Med 1931;3:102. (cited by Larsson et Sjogren, ref. 2) 25. Yanagisawa N, Goto A, Narabayashi H. Familial dystonia musculorum deformans and tremor. J Neurol Sci 1971;16: 125-36. 26. Marsden CD, Marion MH, Quinn N. The treatment of severe dystonia in children and adults. J Neurol Neurosurg Psychiatr 1984;47:1166-73. 27. Fahn S. High dosage anticholinergic therapy in dystonia. Neurology 1Y83;33:1255-61. 28. Klawans HL, Glantx R, Tanner CM, Goetz C. Primary writing tremor: a selective action tremor. Neurology 1982;32: 2034 29. Ravit S, Hallett M, Baker M, Wilkens D. Primary writing tremor and myoclonic writer’s cramp. Neurology 1985;35: 1387-91. 30. Cohen L, Hallett M, Sudarsky L. A single family with writer’s cramp, essential tremor and primary writing tremor. Mov Disord 1987;2:109-16. 31. Rivest J, Marsden CD. Trunk and head tremor as isolated manifestations of dystonia. Mov Disord 1990;5:6&5. 32. Ozelius L, Kramer P, Moskowitz C, et al. Human gene for torsion dystonia located on chromosome 9q32-q34. Neuron 1989;2:1427-34.
Tremor and Idiopathic Dystonia C. P. Jedynak, *A. M. Bonnet and "Y. Agid Centre Medico-Chirurgical Foch, Suresnes, and *Clinique de Neurologie et de Neuropsychologie and INSERM U.289, Hdpital de la SalpCtriere, Paris, France
Summary: The clinical and electromyographic characteristics of tremor were studied in 45 patients presenting with various forms of idiopathic dystonia. Dystonic tremor was shown to be postural, localized, and irregular in amplitude and periodicity, absent during muscle relaxation, exacerbated by smooth muscle contraction, and associated frequently with myoclonus. Although it resembles essential tremor, dystonic tremor seems to be a distinct entity: it is more irregular with a broader range of frequencies; it is asymmetric and remains localized; myoclonus is sometimes associated. This type of tremor is most often seen in the presence of dystonia, but may be observed without evident dystonic symptoms. Key Words: Tremor-Idiopathic dystonia.
The initial description of dystonia musculorum deformans by Oppenheim (1) associated tremor with the dystonic symptom. A high proportion of tremor was observed among patients with the familial form of the disease examined by Larsson and Sjogren (2). In all the patients that Yanagisawa examined by electromyography (EMG), dystonia was associated with rhythmic activity (3). In a study of generalized nonfamilial idiopathic dystonia, 14% of the patients presented with tremor (4). Tremor has also been observed in focal forms of the disease ( 5 ) . Among 132 patients with spasmodic torticollis studied by EMG (6), rhythmic activity was observed in 40% of the cases and tremor of the upper limbs in 21%. Tremor of the hand used for writing has been reported in almost half of the subjects with writer's cramp that have been studied (7,8). Thus, tremor, most often qualified as essential tremor, accompanies dystonia, whether it be generalized, segmental or focal, sporadic or hereditary. Conversely, the presence of focal dystonia is regularly observed in studies of essential tremor. Spasmodic torticollis accompanies essential tremor in about 10% of cases (9,lO); a figure of 3% was re-
ported in the Rochester epidemiological study (11). Writing tremor may be categorized somewhere between idiopathic dystonia and essential tremor (12). According to Rothwell et al. (13), it has a character of its own and differs from benign essential tremor, which is devoid of dystonic elements. In the present study, we have determined the clinical and electromyographic characteristics of tremor observed in generalized, segmental, and focal forms of idiopathic dystonia.
PATIENTS Forty-five patients were studied between 1977 and 1987, 32 in the electrophysiology laboratory of the SalpCtribre Hospital (Paris) and 13 at the C.M.C. Foch (Suresnes, France). Dystonia was diagnosed by clinical observation and EMG. Despite clinical similarities with idiopathic forms of the disease, secondary dystonias were excluded. Patients presenting with various forms of idiopathic dystonia who complained of tremor were included in the study, and were divided into two groups according to the type of tremor and the territory affected. A third group of patients, included for comparison, had tremor with electromyographic features similar to those of the other patients, but no observable dystonic symptoms.
Address correspondence and reprint requests to Dr. P. Jedynak, CMC Foch, 92150 Suresnes, France.
230
TREMOR AND IDIOPATHIC D YSTONIA
Group I Generalized and Segmental Dystonias
231
cases, where the tremor or dystonia affected more than the selective hand and function, were of early onset. None of the patients in this group reported affected family members.
Group I was composed of 10 patients (Table 1). Dystonia was generalized in three cases, and affected the face, neck, upper members, and trunk in four other cases, sparing the pelvis and lower limbs. A single limb was affected in three patients. In one case, dystonia was limited to one lower limb. Two patients had familial dystonia, and three patients mentioned tremor in near relatives.
Group 111: Focal Tremor without Concomitant Symptomatic Dystonia This group was composed of eight patients (Table 3), five of whom had selective writing tremor, and three of whom had tremor of the neck. No tremor of the upper limbs or the voice was observed. The sister of one of the patients also had cervical tremor, and another patient came from a family with a history of focal dystonias including blepharospasm and a case of spasmodic torticollis.
Group 11: Focal Dystonias Twenty-one patients presented a clinical picture in which spasmodic torticollis predominated (Table 2). In seven cases, cervical dystonia also encompassed the scapular muscles. In three cases, dystonia also affected the upper members, but to a lesser degree. In 10 of the 21 patients, the tremor affected one or both upper limbs. In one case (no. l l ) , spasmodic torticollis was associated with writing tremor, without dystonia of the hand. Four patients described contraction of the hand while writing, and four reported tremor in a parent. Eight other patients who had predominant focal dystonia of the hand (Table 2) complained mainly of functional tremor: in the right hand when playing the piano in one case, and while writing in the others. The dystonic cramps and tremor were associated with difficulty in executing fine movements in one patient, dystonic posture of the whole upper limb while walking in another, and postural tremor of the fingers and the hand in two others. These
METHOD For each patient, in addition to the anamnesis and clinical examination, EMG activity was recorded with surface electrodes placed on the muscles involved in the abnormal movement. Activity from a minimum of two pairs of muscles was recorded, except for the functional dystonias, where at least one agonist-antagonist pair was studied. Tremor was evidenced on the EMG and on the accelerometer trace. The protocol included study of (a) spontaneous activity at rest; (b) factors that modify the intensity of the activity (mental calculation, voluntary movement of another segment of the body, antagonistic movement); (c) maintenance of imposed
TABLE 1. Tremor in patients with generalized and segmental dystonias Age (yr)
Onset age (yr)
Patient
Sex
1 2 3 4
F F F M
33 20 62 31
17 15 59 12
5
M
29
6
6 I
M F
30 16
15
8 9 10
F F F
59 16 34
49
14 15
30
Dystonia
Tremor
Site
Intensity"
Siteb
Intensity"
Frequency (Hz)
Myoclonus
Gen. Gen . Gen. Right arm, face, neck Arms, face, neck, larynx Arms, neck Right arm, neck Right arm Left leg Right arm
++++
Right arm Right arm Left arm Right arm
+ ++ ++ +++ ++ + ++ ++ +++ +++
> 12
-
++++ ++ ++ ++
Right arm
+++ ++
Right arm Right arm
++
Right arm Left leg Right arm
+ +
5 9-10
+ -
6
-
4
-
8
-
-d 5-9 5.5 10
+ + -
-
Gen., generalized. a Scored + to + + + (see ref. 15). Site of electromyogram recording. +, 1 g. Nonperiodic; frequency indeterminable.
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C . P.JEDYNAK ET AL.
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TABLE 2. Tremor in patients with .focal dystonias
Patient
Age (yr)
Sex
Neck-predominant 11 F 12 F 13 M
Dystonia
Onset age (yr)
tremor 23 30 42
6 29 38
Site
Intensity
Site
+++ ++ +++ ++ + + + ++ ++ ++ ++ ++ ++ + +++
Right armc Right arm Neck
14
F
35
35
15
M
31
30
16 17 18 19 20 21 22 23 24 25 26 27
M F F M M M
F
35 32 35 25 67 65 30 69 42 52 29 38
15 31 25 21 66 58 9 59 37 49 24 20
Neck Neck, scap Neck, scap, right arm Neck, scap, arms Neck, scap, left arm Neck Neck Neck, scap Neck, scap Neck Neck Neck Neck Neck Neck Neck Neck
28 29
M F
46 51
45 48
Neck Neck
30 31
F
67
64
M
44
42
Neck Neck
F F F F M
Patient
Sex
Age (yr)
Tremor
++ ++ +++ ++ ++ +++
Neck Neck Right arm Neck Arms Neck Neck Neck,d right arm Right,d left arms Neck, left armd Neck Neck Neck, right armd Neck, right,d left arms Neckd Right, leftd arms, legs Neck Neck, right,d left arms
20
33 34
M M
68 25
63 10
35
M
34
8
36
F
63
54
37 38 39
M F M
23 43 52
10 30 52
Frequency (Hz)
+ ++ ++ + + +++ ++ ++ + ++ ++ ++ ++ +++ + ++ +++ + ++ + +
6 10 10 >10
I 8 5 > 12 7 6 5 5 -e 8 5
> 12 10 10 10
Tremor
Onset age (yr)
Hand-predominant tremor 32 M 20
Intensity
Writer’s cramp, fine movements Instrumental cramp (piano) Writer’s cramp, dystonia (right arm) Writer’s cramp, postural tremor (right arm) Writer’s cramp, postural tremor (arms) Writer’s cramp Writer’s cramp Writer’s cramp
Intensity
Frequency (Hz)
Myoclonus
++ + + + ++ ++ ++ ++
5
-
6 10
+
6
-
7
-
4.5 8-12
+ +
-d
-
scap, scapular arch. Scored + to + + + (see ref. 15). b + , 1 g. Writing tremor. Site of electromyogram recording. Nonperiodic; frequency indeterminable. a
++
postures; and (d) voluntary movement and passive movement imposed by the examiner. The shortening reaction (14) was elicited. Muscular activity was recorded with an electroencephalograph. The intento sity of dystonic activity was scored from + + (15). The intensity of tremor was measured by the accelerometer and scored + , , or
+
+
Movement Disorders, Vol. 6 , No. 3, 1991
+ ++
+++
, according to whether acceleration was I g. Myoclonus was defined as abrupt muscular contractions, isolated in a given limb or synchronously involving an agonistantagonist couple, that are repeated with no definite period or with a frequency S3 Hz, in which case it no longer has the appearance of tremor.
TREMOR AND IDIOPATHIC DYSTONIA
233
TABLE 3. Focal tremor without concomitant symptomatic dystonia
Patient
Sex
Age (yr)
40 41 42 43 44 45 46 47
F M M M M F F F
55 63 20 43 52 68 64 62
a
Tremor
Onset age (yr)
Site
Intensitya
54 60 20 ? 51 61 46 55
Writer’s tremor Writer’s tremor Writer’s tremor Writer’s tremor Writer’s tremor Head tremor Head tremofl Head tremorC
+ ++ ++ ++ ++ +++ + ++
Frequency (Hz)
Myoclonus
6-7 7 7 7
-d 4-6 4.5 4.5
+, 1 g. A sister also had head tremor. Familial focal dystonia. Nonperiodic; frequency indeterminable.
RESULTS The results for the three groups of patients are presented in Tables 1-3. Involuntary muscular activity has been analyzed according to the type of movement (tremor, myoclonus, or dystonia) and the circumstances in which it appears. Types of Abnormal Movements Tremor Tremor was observed in all patients. Most often it was The amp1itude and duration Of each burst of contraction were variable and differed from preceding Or succeeding bursts. In agonistantagonist COUPh repetitive bursts did not alternate, but seemed rather to be imperfectly sYnchronized. The mean frequency of the tremor in a given segment (neck or arm) was constant in a given patient, but could vary among segments (e.g., patient 15). The frequency varied among patients from 4 to 12 Hz, and was often situated between 6 and 8 Hz. At neck level, slower or faster frequencies were observed. Above 10 Hz, rhythmic activity of what ap-
peared to be continuous muscle contractions could be detected only by EMG. In general, these tremors could be stopped by strong voluntary or involuntary contractions of the affected muscles. For example, in a form of spasmodic torticollis with tremor, the tremor-inducing activity was attenuated or disappeared when the head of the patient was involuntarily or forcibly turned, but reappeared or increased when the head was held straight (Fig. 1). Tremor was strictly localized. In the neck, it affected the rotator but spared the phonator muscles. voice tremor never occurred in spasmodic torticollis of the tremor type. Tremor of the upper limbs often spared the neck, and always spared the lower limbs and voice. The tremor that accompanied writer’s cramp was always located in the hand used for writing, sparing the root of the limb and contralateral upper limb. MYoclonus Myoclonus was observed in 14 patients distributed among the three groups. The bursts of contraction were highly variable, but always lasted >80 ms
R Splenius c .
FIG. 1. In this patient with right-oriented spasmodic torticollis (case 24), the tremor, which occurs preferentially in the left sternomastoid muscle where dystonia is predominant, appears when the head is intentionally held straight.
Sternornast. Sternornast.
L Splenius c.
Turned to the Right.
Straight.
to the left
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C.P . JEDYNAK ET AL.
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(250 on the average). Both tremor and myoclonus could occur together in the same muscle whether in the neck (Fig. 2) or in the limbs. Dystonia Continuous or discontinuous involuntary muscle contractions were present in all the patients of groups I and 11. When continuous, the contractions were reinforced by spontaneous or provoked spasms lasting several seconds. Discontinuous contractions consisted of spasmodic bursts lasting from a half to several seconds, separated by periods of silence. The interplay between agonist and antagonist muscles was disturbed. Voluntary contractions of agonist muscles were abnormally large in amplitude, and antagonist activity persisted instead of being inhibited. The shortening reaction was elicited by passive movement. Appearance of Abnormal Movements When upper limbs were affected, tremor or myoclonus usually appeared during muscle contraction, regardless of whether it involved a movement, maintenance of a position, or a gesture. It should be noted that in the latter case, the abnormal movement was reinforced both when the gesture was initiated and when it approached its goal. Intention played only a moderate role. When myoclonic activity was ample, it could be observed at rest, and was facilitated by emotion or the presence of the examiner. Tremor and myoclonus affecting the cervical muscles could be observed in the patients while seated, in the absence of any activity. Rotation of the neck, either voluntary or caused by a dystonic
spasm, generally eliminated the tremor or the myoclonus. Among focal dystonias, writing or playing a musical instrument triggered the dystonia, tremor, or myoclonus, either immediately or after a few seconds. DISCUSSION In some patients, tremor was present in the territory of the dystonic symptom. This was the case, for example, when spasmodic torticollis was accompanied by tremor of the head, or when writer's cramp was associated with tremor of the hand. In other cases, when spasmodic torticollis was associated with writing tremor or tremor of the hands, the focal dystonia and the tremor were distant from each other. The third group of patients had no dystonic symptoms. In all the cases studied, however, the characteristics of the tremor, which we purposefully call dystonic, were similar with respect to location, frequency, periodicity and the circumstances in which it appeared. The main characteristics of dystonic tremor are as follows. (a) It is a postural tremor, frequently associated with myoclonus. (b) It is localized and irregular in amplitude and periodicity. (c) It disappears when the muscle is relaxed. (d) It appears with muscle contractions needed to maintain a position or perform movements not requiring intense muscular effort. It is a postural tremor. These observations raise several questions concerning the relation between dystonic tremor and myoclonic dystonia, the respective roles of dystonic and essential tremor in postural tremor, and the existence of isolated dystonic-like tremor in the absence of dystonic symptoms.
l&secToop 1
R
Splenius c.
R
Sternomast.
L Sternomast.
L
Splenius c.
Accel. l g [
Movement Disorders, Vol. 6 , No. 3, 1991
FIG. 2. Myoclonus in the same muscle where tremor was recorded a few seconds earlier (case 21).
TREMOR AND IDIOPATHIC D YSTONIA Dystonic Tremor and Myoclonus The notion that tremor often accompanies idiopathic dystonia is uncontested, even if the prevalence of the association is controversial. High figures, on the order of 80%, were advanced by Larsson and Sjogren (2) for generalized dystonia, and by Couch et al. ( 5 ) for spasmodic torticollis. Figures in the range of 15% (1) to 40% (6) are more common. This tremor, considered to be authentic, is often termed essential tremor. The two groups of dystonic patients studied all complained of tremor (the criterion of inclusion) that was confirmed clinically and recorded by EMG. However, some features of this tremor, irregular period and partially synchronized bursts of synergistic muscles, resemble myoclonus. Myoclonic dystonias have also been reported by Obeso et al. (16). Is there a difference between dystonic tremor and myoclonic dystonia? In the former, the activity is rhythmic and appears when a posture is assumed. In the latter, the bursts of muscular activity can be recorded even at rest, although they are facilitated by postures and movements, and recur at irregular intervals. Intermediate forms exist, however. In the group of patients studied by Obeso et al. (16), the myoclonus was rhythmic in one case. In our series, myoclonus was present in addition to tremor in a third of the patients. Tremor and myoclonus could appear successively in the same muscle during the same examination. However, certain dystonic tremors are borderline cases, where the distinction between tremor and myoclonus is difficult to establish. Dystonic Tremor and Essential Tremor A progressive shift in meaning has led to the inclusion of various postural tremors under the term essential tremor. Marsden et al. (17) distinguish several forms of essential tremor: exaggerated physiological tremor, benign and severe essential tremor, symptomatic tremor in peripheral neuropathies, and tremor in dystonia. The heterogeneity of these tremors has been the subject of debate (18). Another classification of postural tremors is possible, restricting the definition of essential tremor. In this case, essential tremor is considered as a disease characterized by isolated tremor, in the absence of any other neurological manifestation (19). In general, tremor is localized at the extremity of the two upper limbs (9), sometimes affecting the neck and the voice. Isolated voice tremor (20), like orthostatic tremor (21), seems to be a clinical vari-
235
ant of the same disease. Absent at rest, tremor of the upper members appears when positions are assumed or during the performance of fine movements like writing. Its frequency reaches a maximum of 6-8 Hz, and is slower on the side where the amplitude of the tremor is greatest (22). The tremor progresses slowly but inexorably, like degenerative diseases. With age, the territory of the tremor becomes more extended, its amplitude increases, and its frequency slows. When severe, it can impede or render impossible the elementary activities of daily life (23). The tremor that accompanies idiopathic dystonia resembles essential tremor because of its postural character, but is distinguished by its clinical and EMG features. The range of frequencies is broader and the tremor more irregular. Myoclonus, never seen in essential tremor, is sometimes present. The site of the tremor and its evolution are different. More localized and less symmetric, dystonic tremor, once established, remains stable as to its site, amplitude, and frequency. Although this type of tremor is usually observed in the presence of dystonia, it may also occur alone, without evident dystonic symptoms (Table 3). In the absence of radiological, biological, or anatomopathological criteria, the distinction between essential and dystonic tremor can be made on genetic grounds. Starting from the initial study of Velander et al. (24), Larsson and Sjogren studied the familial character of essential tremor (19) and dystonia musculorum deformans (2), including a number of forms with tremor. They concluded that there was no relationship between the two diseases. Dystonic Tremor without Dystonic Symptoms In an extensive family of dystonic subjects, Yanigasawa et al. (25) showed that expression of the abnormal gene was sometimes limited to an isolated tremor with no other dystonic symptoms. Because sporadic idiopathic dystonia cannot be distinguished from the hereditary form on the basis of clinical criteria, it is conceivable that other cases of isolated tremor may also be the consequence of dystonic disease. This hypothesis is supported by the similarities observed between tremor in dystonic patients (Tables 1 and 2) and the writing tremor or tremor of the head observed in the absence of dystonic symptoms (Table 3): irregular frequency and period, associated myoclonus , segmental localization, and clinical stability. According to this hypothesis, then, certain writing tremors would
Movement Disorders, Vol. 6 . N o . 3, 1991
C . P . JEDYNAK ET AL.
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be pure forms of writer’s cramp without the dystonic symptom. This was the case with one of our patients with cervical dystonia who had writing tremor but no dystonia of the hand. The efficacy of anticholinergic medication in the treatment of both dystonia (26,27) and writing tremor (28) that resembles myoclonic dystonia (29) also supports this assumption. A case of writing tremor has been reported in a family with focal dystonia (30). A third source of support for the hypothesis is the observation that cervical and truncal tremor sometimes precedes the onset of spasmodic torticollis by several years (31). According to Baxter et al. (lo), the prognosis of certain cervical tremors is compromised by the risk that true spasmodic torticollis will develop. If our hypothesis is correct, this tremor should be considered as an initial manifestation of dystonia. One of our patients with cervical tremor indeed came from a family with focal dystonias. The gene responsible for idiopathic familial dystonia has recently been localized (32), and the genetics of hereditary forms of essential tremor are under study. These studies should show that the tremor observed in idiopathic dystonia is not associated essential tremor, but a form of tremor with its own clinical and EMG features. Tremors with the same characteristics, observed in the absence of symptomatic dystonia, may be due to dystonic disease. REFERENCES 1 . Oppenheim H. Uber eine eigenartige Krampfkrankheit des kindlichen und jungendichen Alters (dysbasia lordotica progressiva, dystonia musculorum deformans). Neuro Cbl 191 1 ;30:1090-107. 2. Larsson T, Sjogren T. Dystonia musculorum deformans. A genetic and clinical population study of 121 cases. Acta Neurol Scand 1966;42(suppl 17):1-233. 3. Yanagisawa N, Goto A. Dystonia musculorum deformans. Analysis with electromyography. J Neurof Sci iY71;13:3965. 4. Marsden CD, Harrison MJG. Idiopathic torsion dystonia (dystonia musculorum deformans). A review of forty-two patients. Brain 1974;97:793-810. 5. Couch JR. Dystonia and tremor in spasmodic torticollis. In: Eldridge R, Fahn S, eds. Advances in neurology. Vol. 14: Dystonia. New York: Raven Press, 1976:245-58. 6. Rondot P, Jedynak CP, Ferrey G, eds. Le torticolis spasmodique. Rapport de neurologie. In: CongrPs de psychiatrie et de neurologie de langue francaise. Paris: Masson, 1981:l57. 7. Rondot P, Jedynak CP. Dystonies de fonction. Neurologie 1976;9:17007 C20. 8. Sheehy MP, Marsden CD. Writer’s cramp. A focal dystonia. Brain 1982;105:461-80.
Movement Disorders, Vol. 6 , N o . 3, 1991
9. Critchley E. Clinical manifestations of essential tremor. J Neurol Neurosurg Psychiatr 1972;35:365-72. 10. Baxter DW, La1 S. Essential tremor and dystonic syndromes. In: Poirier LJ, Sourkes TL, BBdard PJ, eds. Advances in neurology. Vol. 24: The extrapyramidal system and its disorders. New York: Raven Press, 1979:373-7. 1 1 . Rajput AH, Offord KP, Beard CM, Kurland LT. Essential tremor in Rochester, Minnesota: a 45-year study. J Neurol Neurosurg Psychiatr 1984;47:466-70. 12. Rosenbaum F, Jankovic J. Focal task specific tremor and dystonia. Neurology 1988;38:522-7. 13. Rothwell JC, Traub MM, Marsden CD. Primary writing tremor. J Neurol Neurosurg Psychiatr 1979;42:1106-14. 14. Rondot P, Scherrer J. Contraction rBflexe provoqute par le raccourcissement passif du muscle dam l’athttose et les dystonie d’attitude. Rev Neurol 1966;114:329-336. 15. Burke RE, Fahn S, Marsden CD, Bressman SB, Moscowitz C, Friedman J. Validity and reliability of a rating scale for the primary torsion dystonias. Neurology 1985;35:73-77. 16. Obeso JA, Rothwell JC, Lang AE, Marsden CD. Myoclonic dystonia. Neurology 1983;33:825-830. 17. Marsden CD, Obeso J, Rothwell JC. Benign essential tremor is not a single entity. In: Yahr MD, ed. Current concepts in Parkinson’s disease. Amsterdam: Excerpta Medica, 1983: 3146. 18. Elbe RJ. Physiologic and essential tremor. Neurology 1986; 36:225-231. 19. Larsson T, Sjogren T. Essential tremor. A clinical and genetic population study. Acta Psychiatr Neurol Scand 1960; 3 6 ( ~ ~ p 144): p l 1-1 76. 20. Hatchinsky VC. The nature of primary vocal tremor. Can J Neurol Sci 1975;2:195-197. 21. Heilrnan KM. Orthostatic tremor. Arch NeurollY84;41:880881. 22. Homberg V, Hefter H, Reiners K, Freund HJ. Differential effects of changes in mechanical limb properties on physiological and pathological tremor. J Neuiol Neurosurg Psychiatr 1987;50:568-79. 23. Koller WC, Biaryn, Rubino FA. Essential tremor variants. Neurology 1986;36(suppl 1):121-2. 24. Velander F. Arftlighetestudier inom trenne slakter med hereditar tremor. Nord Med 1931;3:102. (cited by Larsson et Sjogren, ref. 2) 25. Yanagisawa N, Goto A, Narabayashi H. Familial dystonia musculorum deformans and tremor. J Neurol Sci 1971;16: 125-36. 26. Marsden CD, Marion MH, Quinn N. The treatment of severe dystonia in children and adults. J Neurol Neurosurg Psychiatr 1984;47:1166-73. 27. Fahn S. High dosage anticholinergic therapy in dystonia. Neurology 1Y83;33:1255-61. 28. Klawans HL, Glantx R, Tanner CM, Goetz C. Primary writing tremor: a selective action tremor. Neurology 1982;32: 2034 29. Ravit S, Hallett M, Baker M, Wilkens D. Primary writing tremor and myoclonic writer’s cramp. Neurology 1985;35: 1387-91. 30. Cohen L, Hallett M, Sudarsky L. A single family with writer’s cramp, essential tremor and primary writing tremor. Mov Disord 1987;2:109-16. 31. Rivest J, Marsden CD. Trunk and head tremor as isolated manifestations of dystonia. Mov Disord 1990;5:6&5. 32. Ozelius L, Kramer P, Moskowitz C, et al. Human gene for torsion dystonia located on chromosome 9q32-q34. Neuron 1989;2:1427-34.
