LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES

Pathophysiology and Pharmacotherapy of Spasmodic Torticollis: A Review

S. LAL

SUMMARY: The few existing neuropa- ive evaluation of response, documentation INTRODUCTION thological, neurochemical, and neurophar- of key data, and adequacy of duration of "Spasmodic torticollis is an invo­ acological studies have shed little light follow-up make interpretation of published luntary hyperkinesis manifesting itself on the pathophysiology of spasmodic tor­ results difficult. Because of the heteroge­ ticollis (ST). The relevance of experimen­ neity of ST, investigations aimed at esta­ by mobile, tonic or clonic spasms of tal ST in animals and drug-induced ST in blishing a neurotransmitter profile for each the neck musculature, and producing a man to idiopathic ST is unclear. patient by observing the acute response to more or less stereotyped deviation of Most pharmacotherapeutic endeavors a test dose of drugs affecting cholinergic, the head into an abnormal position, have focused on drugs affecting basal gan­ dopaminergic, serotonergic, and gamma- the chin being rotated to one side or glia function. Unfortunately, problems of aminobutyric acid systems may provide a the head bent directly forward (ante- sample size, clinical heterogeneity of pa­ more rational basis to the selection of treat­ collis) or backward (retrocollis)" (Pat­ tient population, research design, object- ment. terson and Little, 1943). The etiology and site of a presumed central nervous system (CNS) lesion is unknown. Most pharmacotherapeutic endeavors have RfiSUMfi: Les rares etudes neuro- blies alleatoire: grandeur de I'echantillon- focused on drugs that affect basal gan­ pathologiques, neurochimiques et neuro- nage, heterogeneite clinique des popula­ glia function. Unlike Parkinson's dis­ pharmacologiques connues ne jettent que tions, plans de recherches, evaluation ob­ peu de lumiere sur la physiopathologie du jective des reponses, documentation de ease and Huntington's chorea where torticollis spasmodique (ST). La corres- donnees-clef, pertinence de la dure'e anatomical, chemical, and pharmaco­ pondance entre le ST experimental chez d'observation. A cause de I'heterogeneite logical information may provide a ra­ I'animal, le STinduitpardes medicaments, du ST, nous croyons qu'une batterie de tional basis for therapy, such an under­ et le ST idiopathique humain est encore tests qui aurait pour but d'evaluer, chez pinning of knowledge in spasmodic inconnue. chaque patient, la reponse aigu'i a des torticollis (ST) is lacking. Drug treat­ La plupart des essais pharmacothera- doses-essai de divers medicaments choli- ment is both advanced and discounted peutiques se sont concentres sur les medi­ nergiques, dopaminergiques, serotoniner- yet published results are few, contra­ caments agissant sur les fonctions des no- giqueset GABAergiques, offrirait unebase dictory, poorly controlled, and often yaux gris centraux. Plusieurs problemes plus valable pour la selection du traite- inadequately documented. rendent I'interpretation des resultats pu- ment approprie. The present paper discusses the pa­ thophysiology of ST and reviews in detail the available literature on the pharmacotherapy of this disorder.

PATHOPHYSIOLOGY OF ST /. Neuroanatomical findings Psychological factors play a doubt­ ful role in the etiology of ST (Marsden, 1976; Mathews et al., 1978; Cockburn, 1971; Choppy-Jacolin et al., 1977). On the other hand, demonstration of a consistent pathological lesion remains elusive. Necropsy studies have been few. Lesions in the striatum, amongst other sites, have been described in From the Department of Psychiatry, Montreal Gen­ eral Hospital, Montreal three autopsied brains (Grinker and Walker, 1933; Foerster, 1933; Alpers Reprint requests to: Dr. S. Lai, Department of Psy­ chiatry, Montreal General Hospital, 1650 Cedar Street, and Drayer, 1937) as well as in two Montreal, Quebec H3G IA4, Canada. cases in which ST was part of a genera-

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lized dystonia (Cassirer, 1922; Wim- neuro-transmitter metabolism. Cur- nergic agents and drugs that enhance mer, 1929). However, the relevance of zon (1973) found a normal mean gamma-aminobutyric acid (GABA) these findings to the development of concentration of homovanillic acid function improved ST. ST is questioned (Tarlov, 1970). ST (HVA) and 5-hydroxyindoleacetic acid In the marmoset, in which the as­ has been associated with injury to the in lumbar cerebrospinal fluid (CSF) of cending DA fibers projecting from the cerebral cortex (David et al., 1952), 9 patients, whereas in a single case mesencephalic tegmentum to the colloid cyst of the third ventricle reported by Johansson and Roos ipsilateral striatum were lesioned with (Avman and Arasil, 1969), as well as (1974) there was a lowered value of 6-hydroxy-DA, amphetamine, an in­ with posterior fossa tumors (Winther, both acids. In ventricular CSF from 4 directly acting DA receptor agonist, 1930; Boisen, 1979). In the latter, patients with ST and 2 with dystonia worsened ST. Low doses of apomor­ clonic features were not described. musculorum deformans, HVA con­ phine, which may inhibit DA neuro­ These symptomatic cases may indicate centrations were intermediate between transmission (in contrast to large that lesions at several levels of the CNS non-neurological controls and Parkin­ doses, Tolosa, 1978), alleviated the may induce a clinical picture of ST. sonian patients (Papeschi et al., 1972). experimental condition. High doses of However, in the majority of cases of apomorphine reversed the direction of ST there is no demonstrable lesion. 4. Endocrinological findings in ST ST (Crossman and Sambrook, 1978). Hassler and Dieckman (1970) found ST may develop as a consequence of In the mid-brain lesioned cat the significant differences in cerebral hyperthyroidism and resolve with 5HT precursor, 5-hydroxytryptophan, hemispheric size on pneumoencepha­ treatment of the endocrine dysfunc­ worsened ST and L-dopa had no effect lography in 85% of cases. They specu­ tion (Gilbert, 1972a). Thyroxine in­ (Mori et al., 1975). lated that these radiological findings creases catecholamine receptor sensi­ indicated early brain damage which tivity, but whether such a mechanism 6. Drug-induced ST in man destroyed parts of the putamen (or accounts for the precipitation of ST in Neuroleptics (Ayd, 1961) as well as projections to the putamen) which a predisposed individual remains the benzamide derivative, metoclo- exert an inhibitory effect on contra- conjectural. In a single case of ST, pramide (Casteels-van Daele et al., versive head movements. This inhibi­ apomorphine, a DA receptor agonist, 1970) block DA receptors and induce a tory action may become ineffective failed to increase growth hormone variety of dystonic reactions including and ST become manifest. Unfor­ secretion (Brown et al., 1973). The ST in the early stages of treatment. tunately, the incidence of hemispheric significance of this isolated finding is Clinically, acute drug-induced ST is asymmetry in subjects without ST was unclear. predominantly tonic in nature. Swett not given. (1975) reported torticollis occurring in 5. Neuropharmacological studies in ex­ 35 out of 1152 patients receiving neu­ 2. Experimental ST perimental ST roleptics. In 20 cases of acute pheno- Focal brain stems lesions have been Neurotransmitter dysfunction has thiazine toxicity in childhood, four known to produce abnormal neck been investigated in experimental ST, had torticollis (Gupta and Lovejoy, postures in experimental animals but results do not lend themselves to 1967). These dystonic reactions res­ (Foltz et al., 1969; Carpenter, 1956; ready conclusions. Based on experi­ ponded rapidly to anticholinergic Denny-Brown, 1962; Poirier, 1960; ments in the monkey (Macaca mulat- agents (DiMascio et al., 1976), anti­ Mori et al., 1975; Battista et al., 1976; ta), in which ST was produced by elec­ histamines (Gupta and Lovejoy, Carrea and Mettler, 1955). Interrup­ trolytic lesions in the mesencephalic 1967; Cottom and Newman, 1966), tion of ascending dopamine (DA) tegmentum, Foltz et al. (1959) pos­ which are also potent anticholinergic fibers from the midbrain tegmentum tulated that a denervation hypersen­ agents, as well as to the indirectly in the marmoset induces severe torti­ sitivity of acetylcholine neurons which acting DA receptor agonists, aman­ collis with deviation of the head control postural movements of the tadine (DiMascio et al., 1976) and towards the side of the lesion, but head and neck was important in the methylphenidate (Fann, 1966). lesions in the pontine tegmentum, genesis of ST. However, anticholi­ ST may also develop as an isolated which affect ascending noradrenergic nergic agents failed to improve the complication of chronic neuroleptic neurons, induce contralateral torti­ experimental disorder. Anticholiner­ therapy (Chateau et al., 1966; Ha- collis (Crossman and Sambrook, gics, L-dopa, piribedil (indirectly renko, 1967) and can be considered as 1978). Tarlov (1970), examined brain acting DA receptor agonists), and a form of tardive dyskinesia. However, regions that have been implicated in apomorphine were ineffective in im­ whether chronic neuroleptic-induced the experimental pathophysiology of proving ST induced by ventromedial ST pharmacologically resembles the ST, but found no histological abnor­ mesencephalic tegmental lesions in the more commonly studied oral form of malities in the single ST brain investi­ African green monkey (Battista et al., tardive dyskinesia [i.e. worsening with gated. 1976). Worsening of symptoms with anticholinergics and DA activating these agents was not described. On the agents, but improvement with choli­ 3. Biochemical studies in ST other hand, the DA receptor blockers nergics and drugs that impair DA The absence of anatomical changes haloperidol or pimozide, the catecho­ function (Marsden et al., 1976)] which does not exclude a biochemical lesion. lamine synthesis inhibitor, alpha- is the opposite of acute neuroleptic- A few investigations have focused on methyl-para-tyrosine, as well as choli­ induced ST, has not been well studied.

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In a single case, doses of neuroleptic 1971). Unfortunately, the diagnosis in (Hi) research design sufficient to induce Parkinsonism this single case report remains in Evaluation of treatment should take eliminated chronic neuroleptic-induced doubt. Meprobamate administered into account the natural history of the ST (Chateau et al., 1966). "Parkinso­ over two days in combination with disorder. Meares (1971), in a retros­ nism medication" was ineffective in 6 behavior therapy has resulted in pective study, observed 4 remissions patients with retrocollis associated amelioration in one patient (Turner et lasting 18 mos - 29 yrs in 24 with chronic neuroleptic use (Haren- al., 1974), but improvement continued unoperated patients during the first ko, 1967). with behavior therapy alone. year of the disorder and Mathews et In addition to chronic neuroleptic al (1978) reported complete or sub­ treatment which is believed to induce stantial remission in 5 out of 30 striatal DA super-sensitivity (Marsden PHARMACOTHERAPY OF patients in the first year of illness. et al., 1975), chronic treatment with L- IDIOPATHIC ST Beyond a year of the disorder, sponta­ dopa, in Parkinsonian patients at /. General Comments neous remissions are still possible least, may also induce ST (Barbeau et Table 1 summarizes the findings of (Meares, 1971; Mathews et al., 1978). al., 1971; Sigwald and Raymondeaud, 42 drug treatment trials reported in 33 In addition, fluctuations in intensity of 1970). This may suggest that enhanced papers published between 1937-1978 the symptoms may vary from day to DA function induces ST. However, involving approximately 148 indivi­ day or hour to hour. Also, the invo­ improvement of acute neuroleptic- duals. It would appear that 64 of the luntary movements are sensitive to induced ST with drugs that enhance patients derived clinically significant stress as well as to a variety of sensory DA function points to the complexity improvement with drug therapy. Un­ stimuli (Podvinsky, 1969; Herz and of relating drug-induced ST to idiopa­ fortunately, the data are limited in Glazer, 1949). Hence, in the absence of control procedures, interpretation of thic ST. Nevertheless, drug-induced many respects and problems of inter­ results is difficult. Of 42 drug treat­ dystonic reactions resemble sponta­ pretation are many. ment reports in Table 1, only 2 have neously occurring movement dis­ (i) sample size utilized a double-blind placebo- orders (Marsden et al., 1976; Ayd, ST is a relatively uncommon dis­ controlled technique (West, 1977; order, though basic data on the 1961) so that it is difficult to believe Couch, 1976a). In both, a cross-over incidence and prevalence are un­ that they are entirely without rele­ design was used. In a further 6 reports, known. Of 42 drug treatment trials, 17 vance to the pathophysiology of placebo substitution was used but not described results in only 1 or 2 idiopathic dystonias, including ST. systematically in all individuals. In 2 patients, 16 in 5 or more and of the other reports, the design involved latter only 5 reported on series of 10 or 7. Neuropharmacologies studies in idio­ placebo substitution but only if more subjects. pathic ST improvement occurred. In an addi­ (ii) clinical heterogeneity Few data are available on the effect tional 8 reports, the effect of dose of test doses of drugs on ST. Hirsch- In a variable number of patients reduction or drug discontinuation was mann and Mayer (1964) in an open with ST there is a family history of described but not in all subjects. The study found that L-dopa (25 mg iv) essential tremor, coexisting signs of study of Couch (1976a) is the only one improved all 6 patients with ST essential tremor, facial spasms and which provides a statistical analysis of including one subject who had asso­ tics, extranuchal dystonic features, results. ciated truncal dystonia. Surprisingly, and Parkinsonian symptoms (Patter­ the beneficial effects lasted up to three son and Little, 1943; Couch, 1976b; Only in exceptional cases are treat­ days. Tolosa (1978), in a predomi­ Marsden, 1976; Critchley, 1939). In ment observations beyond 3 mo nantly uncontrolled investigation, no­ others there is a history of encepha­ described. In only 7 patients has this ted transient improvement (45-60 litis (Patterson and Little, 1943) or the extended to 1 year or more and of mins) in 2 out of 7 patients following ST is a manifestation of idiopathic these in only 2 subjects was the effect apomorphine (1-3 mg sc). In a placebo- torsion dystonia (Marsden, 1976). In of drug discontinuation, dose reduc­ controlled observation with film re­ addition, abnormal CSF protein pat­ tion, or placebo substitution reported. cording in one patient and uncon­ terns are found in some patients but (iv) objective evaluation of improvement trolled observations in another, am­ not in others (Kjellin and Stibler, Objective assessment of severity of phetamine (30 mg im) induced im­ 1975). Studies on ST include a mixture ST is difficult and evaluation is usually provement within 30 mins on several of patients from this broad clinical limited to clinical impression. Colla­ different occasions which lasted 18-24 spectrum. How far this heterogeneity teral information is sometimes sought hrs. (Myerson and Loman, 1942). reflects different etiologies of ST or (West, 1977). Couch (1976a) used a These three reports suggest that in accounts for dramatic responses to clinical rating scale of frequency and some patients DA function is im­ pharmacotherapy in some patients but severity of symptoms and Tolosa paired. lack of response in others is unknown. (1978) recorded the duration of Improvement has also been noted Also, how far the inclusion of post- keeping the head vertical. Film has after diazepam (5 mg iv), which thalotomy cases influences outcome to been used in a few studies but only enhances GABA function, but not the drug treatment is uncertain. In many Swash et al. (1972) and Turner et al. antihistamine, diphenhydramine (50 reports little or no clinical data are (1974) described the method or mg iv), (Bianchine and Bianchine, given (Table 1). process of evaluation. Filming permits

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TABLE 1. Pharmacotherapy of Spasmodic Torticollis (ST)

Treatment Dose1 N4 Results OBS6 Comments7 Authors

1. Anti-cholinergics Scopolamine 7 1 Appreciable 7 Post-encephalitic parkinsonism Urechia & improvement Retezeanu, 1937 Scopolamine 7 17 None-slight 7 Patterson & improvement Little, 1943 Atropine (+ Sodium 7 1 Favorable 5-6 mo Duration ST few dy; only partial Krebs, 1939. Iodide) improvement relapse on stopping drug. Miscellaneous Var2 5 lyr Duration ST 4 mo; effect of (CT-237, P-189 2 Sustained stopping drug not reported Cycrimine; improvement Foltz et Scopolamine) 2'^yr Post-chicken pox encephalitis; al., 1959 worsened on dose decrease

3 Transient Dystonia musculorum deformans improvement in 2 Trihexyphenidyl 7 l5 Remitted 6 mo Remission for 10 yr without Barrett et drugs; recurrence refractory al; 1970

2. Cholinergics Deanol 450-900 1 No effect 2 wk Laterre & Fortemps, 1975s

3. Anti-dopaminergics Haloperidol (and/or 1.5-14 7 good or 3 wk-2 yr; In 2 duration of ST «S6 mo; Gilbert, 1971, amantadine 300 mg/dy) excellent <3 mo 2 responded to amantadine alone 1972a, 1972b, 2 no effect in 3 1972c Haloperidol (+ 9-30 2 recovered All familial ST; also on Gilbert 1977a Trihexyphenidyl biofeedback ± Amantadine 2 markedly ± Diazepam) improved Haloperidol 5s No effect Few wk Amantadine failures Bigwood, 1972s Haloperidol 1 dramatic 5 mo Improvement maintained on Shaw et al., improvement stopping drug; worsened on 1972 L-dopa. 5 no effect ? All L-dopa failures Haloperidol 16 8 improved 4 wk Double-blind cross-over; Couch, 1976a 50% +; planned randomization of 6 improved treatment sequence; assess­ 25-50% ment by rating scale 2 no change Prochlorperazine 450 35 Few wk- 1 ? postencephalitic, with Sigwald et All improved 2yr retrocollis al., 1959 Thioproperazine 200 25 Few wk Single blind placebo substi­ Sigwald et al., Both improved tution in 1 1959 Perphenazine 92-108 2 Retrocollis; torsion dystonia; Blom & 1 improved Few wk relapse on dose decrease. Ekbom, 1961 Reserpine 4.5 mg/dy; duration ST 6 mo 1 no effect Pimozide 2' 1 transient Siblings; 1 post-thalotomy Korein, 1977 improvement with segmental dystonia Tiapride 200-500 4 No effect Emile et al., 1977s

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Treatment Dose1 N4 Results OBS" Comments7 Authors

Tiapride 400 45 1 good results 2 mo Trillet et al., 19778 3 no effect <15 2 neuroleptic treatment failures dy-3mo Sulpiride 400 l5 no effect 7 Tiapride failure Trillet et al., 19778 Tetrabenazine 75-200 3 1 improved Swash et al., 1972s 4 wk 'intractable' ST; duration ?; 2 no effect blind film rating Tetrabenazine 150 95 1 transient Shaw et al., improvement 1972 7 All L-dopa failures 8, no effect Reserpine 3-6 25 No effect 27-30 Placebo substitution and Markham et dy filming in responders al., 19638 Alpha-Methyl-dopa 1050 35 No effect 17-28 dy as above Markham et al., 1963s 4. Dopaminergics Amphetamine Responded well ? Chronic encephalitis Patterson & (+ Scopolamine) Little, 1943

Amphetamine 60-120 2 Both marked 5 mo Duration ST 1 mo; relapse Myerson & (+ Scopolamine) improvement on stopping drug. Loman, 1942 (± Nicotinic Acid) 14 mo Both improved with test dose amphetamine Pipradol 35 1 Marked 7 Fabing 1954 improvement Amantadine 300 55 No effect 7-10 dy Haloperidol failures Bigwood, 1972s Amantadine 200 95 1 transient Shaw et al., improvement 1972 2 worsened ? All L-dopa failures 6 no effect Amantadine 200 105 No benefit 1 mo Double-blind cross over. West, 1977 Collateral information. Amantadine (+ 300 35 No benefit Few wk Uncontrolled West, 1977 Haloperidol 6mg/dy) L-Dopa 6-8.5G 35 No effect 1-6 mo Open or single blind placebo Barrett et substitution; film assessment. 1970 2 thalotomy failures L-Dopa Max3 175 1 sustained 2yr Retrocollis Shaw et al., improvement 1972 Placebo substitution and filming in responders. Collateral information. 1 improved but became intole­ rant of L-dopa >4 mo 4 transient improvement 11 no effect ?>1 mo L-Dopa 7.5-8G 6 4 worsened Instrumental measurement Ansari et al.. 83-142 dy of head rotation and tremor. 1972 2 no change

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Treatment Dose1 N4 Results OBS6 Comments7 Authors

Bromocriptine 15-80 10 1 marked Retrocollis. Prior response to Lees et al., improvement L-dopa. Single blind placebo 1976 substitution. 1 worsened >2 mo Improved with haloperidol (4.5 mg/day) - uncontrolled 8 no effect Placebo substitution.

5. Serotonergics L-5-hydroxytryptophan 7 improved -2 wk Stereotactic surgery failures Mori et al., (± Amantadine) 19758

6. Gaba-ergics Diazepam 6-15 6 Excellent 5 dy-6 wk Type of torticollis unspecified. Pernikoff, results 5 'acute', 1 chronic 19648 Diazepam 1 Recovered 2 wk Duration ST 8 days. Improve- Bianchine & ment maintained on stopping Bianchine 1971 drug. L-Glutamine + see text 25 1 symptom Siblings; non-responder post- Korein, 1977 Diazepam + free >2 mo thalotomy and segmental Isoniazid + dystonia Pyridoxine 1 no effect

7. Miscellaneous Lithium serum 3 Striking 1-2 mo Abnormal CSF protein patterns. Kjellin & Li 0.9 improvement Single blind placebo substi­ Stibler, 1975 mM/1 in all tution in 2. Duration ST 2 mo in 1. Lithium 1200 1 Improved few wk Single blind placebo substitu­ Couper- tion; independent evaluators. Smartt, 1973 Prior town gas poisoning & neuroleptic therapy. Lithium ? 2 Both responded ? Gilbert, 1977b Quinine Max3 6 No benefit ? Patterson and Little 19438 Quinine 2G 1 Practically 2 mo Duration ST 3 mos; worse on Hassin, 1939 recovered stopping drug 'Maximum or optimum daily dose in mg/day unless specified. JVarious combinations; names of coded drugs CT-237 and P-189 not given. 'Maximum tolerated dose. 'Number of subjects treated. 'Subjects common to more than one treatment trial administered by the same author. Reports of Shaw et al., (1972) and Lees et al (1976) are based on the same patient population. 'Duration of observations. 'All studies are uncontrolled or presumed uncontrolled unless specified: response evaluated by clinical assessment alone unless specified. "Clinical description or information on duration of ST not given.

frequency counts but amplitude is provement on several measures, name­ sures, side effects reported by the more difficult to assess. Use of a hori­ ly, on clinical assessment, range of patient may be mistaken for worsening zontal grid over a videotape television daily activities, collateral information, of ST. Improvement may result from monitor has been described (Bern­ and an objective recording is required non-specific sedative effects rather hardt et al., 1972), but this has not yet to document improvement, but this is than from a presumed selective been used in pharmacotherapeutic rarely done. pharmacological action. investigations. Ansari and Webster Treatment may result in worsening (1974) described recording devices to of the tonic but improvement of the 2. Effect of anticholinergic agents quantify head rotation and head spasmodic component or vice-versa. Bunts (1960) stated, without details, tremor in ST, but these have not been Whether such change is considered that treatment with anticholinergic widely used (Ansari et al., 1972). amelioration, deterioration, or no drugs (scopolamine, trihexyphenidyl, Unfortunately, a single recording by effect depends on the requirements of and cycrimine) was discouraging and whatever technique may not provide the individual in his day to day Patterson and Little (1943) found an accurate sample of the actual activities. slight to no effect in 17 patients treated treatment response. Sustained im­ In the absence of objective mea­ with scopolamine. In the absence of

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details one can only conjecture that of treatment with the active agent, tution. In one patient, worsening on dose and duration of treatment in the haloperidol, was 4 weeks. The effect of bromocriptine was followed by im­ latter study were adequate. In con­ long-term treatment, however, re­ provement on haloperidol (Lees et al., trast, Putnam et al. (1949) recom­ mains to be documented. The failure 1976). mended atropine for several months with haloperidol reported by some The use of DA activating agents and Poppen and Martinez-Niochet authors (Bigwood, 1972; Shaw et al., resulting in improvement lasting one (1951) suggested scopolamine before 1972) may be due to inadequate doses. or more years has been described in considering surgery. One presumes Gilbert (1972b; 1972c; 1977b) has only 3 patients, one on amphetamine that some patients were improved by emphasized that 14-30 mg or more per combined with scopolamine (Myerson this approach, but the number of day may be needed and in addition co­ and Loman, 1942), one with amanta­ subjects treated and the outcome were administration of amantadine may be dine (Gilbert, 1972a), and one on L- not given. necessary for successful therapy (Gil­ dopa (Shaw et al., 1972). Only in the Mild relief with benztropine has bert, 1972a; 1972c; 1977a). latter was dose reduction, drug dis­ been incidentally noted (Gilbert, 1972a), In 2 patients, one on prochlorper­ continuation, or placebo substitution but otherwise, apart from the single azine (Sigwald et al., 1959) and one on reported. case reports of Barrett et al, (1970) and haloperidol, amantadine and, trihexy­ of Krebs (1939), in whom spontaneous phenidyl (Gilbert, 1972a) improve­ 5. Effect of miscellaneous drugs remissions probably occurred, in only ment for at least 1 year was reported. Evaluation of drugs affecting GABA- 3 patients has improvement been In neither case was the response to ergic or 5HT function have been few. documented with anticholinergics (Ure- drug withdrawal described. The diagnoses in the cases responding chia and Retezeanu, 1937; Foltz et al, It is possible that response to DA to diazepam described by Pernikoff 1959). Interestingly, in 2 of these 3 receptor blockers represents only (1964) and Bianchine and Bianchine patients there was a history of ence­ masking of ST by induction of mild (1971) are unclear. Incidental com­ phalitis. In 2 patients of Foltz et al. drug-induced Parkinsonism. ments pointing to an ineffectual role of (1959), sustained improvement over Results obtained with benzamide diazepam have been mentioned in the one year in 1 patient and 2.5 yrs in the derivatives, depletors of central DA, literature (Barnett et al., 1970; other was described. In the former or alpha-methyldopa show little that is Gilbert, 1972a). Follow-up of the pre­ case, spontaneous improvement can­ encouraging. liminary work of Korein (1977) who not be excluded as a dose reduction used large daily doses of L-glutamine was not tried. In the latter case, several 4. Effect of dopaminergic agents (40G), diazepam (30mg), isoniazid attempts at dose reduction resulted in Putnam et al (1949) and Poppen and (150mg), and pyridoxine (150mg) to relapse. Martinez-Niochet (1951) recommend­ enhance central GABAergic function Anticholinergic drugs have fre­ ed amphetamine as a pharmacological is awaited. quently been used in combination with treatment before considering surgery. All published reports on the use of other pharmacotherapeutic agents to The former used a dose of 10 mg twice lithium have found improvement counteract side effects. The relevance daily. Outcome of this approach was (Kjellin and Stibler, 1975; Gilbert, to therapeutic outcome is difficult to not given. Myerson and Loman (1942) 1977b; Couper-Smartt, 1973) though assess. Myerson and Loman (1942) in 2 patients required considerably long term outcome has not been reported a potentiating effect of larger doses of amphetamine than reported. scopolamine on the beneficial effect of used by Putnam et al (1949) to induce amphetamine in one patient and improvement. In two cases reported POSSIBLE APPROACH TO THE Gilbert (1977b) stated that the thera­ by Gilbert (1972a) amantadine alone TREATMENT OF ST peutic effect of haloperidol was was effective in treating ST. In other The limited and in general poorly reduced by co-administration of anti­ cases combination with haloperidol documented or conducted research cholinergic agents. was necessary. In the only double makes any summary conclusion diffi­ blind study with amantadine no the­ cult. One possible point of focus worth 3. Effect of antidopaminergic agents rapeutic effect was demonstrated considering is that ST is a heteroge­ DA receptor blockers as well as (West, 1977). However, the dose in this neous disorder. This would account directly and indirectly acting DA controlled study was less than that for the diversity of clinical findings as receptor agonists are reported to found successful by Gilbert (1972a; well as the variable pharmacothera­ improve some cases of ST. This 1972b). Studies with L-dopa have peutic responses reported. Some pa­ apparent anomaly is further compli­ involved giving the drug to the tients appear to respond to anticho­ cated by reports that haloperidol in maximum tolerated dose. In general, linergic agents, some to DA receptor combination with amantadine results no effect or worsening has been blockers, and some to DA receptor in marked improvement (Gilbert, reported (Ansari et al., 1972; Shaw et agonists though the total numbers 1972a). The most convincing report of al., 1972; Barrett et al., 1970), though may be small. If this is so then it may a therapeutic benefit from DA recep­ in a single well documented case be possible to identify potential tor blockers was from Couch (1976a) remarkable improvement occurred on responders to these 3 classes of drugs who used a placebo-controlled cross­ both L-dopa and bromocriptine (Lees by observing the response to a single over study in 16 patients. The duration et al, 1976) but not on placebo substi­ dose of benztropine, haloperidol, or

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apomorphine, respectively, under con­ B1ANCHINE, J.R. and BIANCHINE, J. W. CURZON, G. (1973). Involuntary movements trolled conditions. Recent findings (1971). Treatment of spasmodic torticollis other than Parkinsonism: biochemical as­ suggest that a single intravenous dose with diazepam. S. Med. J., 64, 893-894. pects. Proc. Roy. Soc. Med. 66, 29-32. of benztropine and, to a lesser extent, BIGWOOD, G.F. (1972). Treatment of spas­ DAVID, M. HECAEN, H. and CONSTANS, modic torticollis. New Engl. J. Med., 286, J. (1952). Torticolis spasmodique consecutif subcutaneous apomorphine may in­ 1161. a une lesion corticale traumatique. Discus­ deed identify potential responders to BLOM, S. and EKBOM, K.A. (1961). Compa­ sion du resultat favorable obtenu apres chronic benztropine or L-dopa the­ rison between akathisia developing on treat­ excision de la lesion corticale. Rev. Neurol. rapy (Lai et al., 1979). This approach ment with phenothiazine derivatives and (Paris), 86, 57-61. could be extended by evaluating restless legs syndrome. Acta Med. Scand., DENNY-BROWN, D. (1962). The midbrain potential responders to GABAergic 170, 689-694. and motor integration. Proc. Roy. Soc. Med., 55, 527-538. and 5HT drugs by use of a single dose BOISEN, E. (1979). Torticollis caused by an infratentorial tumour. Three cases. Brit. J. DIMASCIO, A., BERNADO, D.L. GREEN- of diazepam or L-tryptophan, respec­ Psychiat., 134, 306-307. BLATT, D. J. and MARDER, J. E. (1976) A tively. Studies establishing an indivi­ BROWN, W.A., VAN WOERT, M.H. and controlled trial of amantadine in drug- dual profile of neurotransmitter func­ AMBANI, L.M. (1973). Effect of apomor­ induced extrapyramidal disorders. Arch. tion by such pharmacological tests phine on growth hormone release in Gen. Psychiat., 33, 599-602. may provide a more rational ap­ humans. J. Clin. Endocrinol. Metab., 37, EMILE, J., BASTARD, J. and TRUELLE, J- proach to the investigation and treat­ 463-465. L. (1977). Utilisation du tiapride en BUNTS, A.T. (1960). The surgical treatment of neurologic Resultats preliminaires. Sem. ment of ST. spasmodic torticollis. Am. Surg., 26, 560- Hop. (Paris), 53, 16-20. 563. FABING, H.D. (1954). Alpha-(2-piperidyl) CARPENTER, M. B. (1956). A study of the red benzhydrol hydrochloride, a new central stimulant, in the treatment of blepharo­ ACKNOWLEDGEMENTS nucleus in the rhesus monkey. Anatomical degenerations and physiological effects spasm, spasmodic torticollis and narcolepsy. This work was supported by the Fund for Research resulting from localized lesions of the red Tran. Am. Neurol. Ass., 79, 159-163. in the Fields of Dyskinesia and Torticollis, Canada. nucleus. J. Comp. Neurol., 105, 195-249. FANN, W.E. (1966). Useofmethylphenidateto CARREA, R.M.E. and METTLER, F.A. counteract acute dystonic effects of pheno- (1955). Function of the primate brachium thiazines. Am. J. Psychiat., 122, 1293-1294. conjunctivum and related structures. J. FOERSTER, O. (1933). Mobile spasm of the Comp. Neurol., 102, 151-322. REFERENCES neck muscles and its physiological basis. J. CASSIRER, R. (1922). Halsmuskelkrampfund ALPERS, B.J. and DRAYER, C.S. (1937). Comp. Neurol. 58: 725-735. Torsionsspasmus. Klin. Wschr., 1, 53-57. The organic background of some cases of FOLTZ, E.L., KNOPP, L.M. and WARD, spasmodic torticollis. Report of a case with CASTEELS-VAN DAELE, M., JAEKEN, J., A. A. (1959). Experimental spasmodic tor­ autopsy. Am. J. Med. Sci., 193, 378-384. VAN DER SCHUEREN, P., ZIMMER­ ticollis. J. Neurosurg., 16, 55-72. MAN, A. and VAN DEN BON. (1970). ANSARI, K.A. and WEBSTER, D. D. (1974). Dystonic reactions in children caused by GILBERT, G.J. (1971). Spasmodic torticollis Quantitative measurements in spasmodic metoclopramide. Arch. Dis. Child., 45, 130- treated effectively by medical means. New torticollis. Dis. Nerv Syst., 35, 44-47. 133. Engl. Med. J., 284, 896-898. ANSARI, K.A., WEBSTER, D. and MAN­ GILBERT, G.J. (1972a). The medical treat­ CHATEAU, R., FAU, R., GROSLAMBERT, NING, N. (1972). Spasmodic torticollis and ment of spasmodic torticollis Arch. Neurol., R. and PERRET, J. (1966). A propos d'un L-dopa. Results of therapeutic trial in six 27, 503-506. cas de torticolis spasmodique irreversible, patients. Neurology, 22, 670-674. survenu au cours d'un traitement par neuro- GILBERT, G.J. (1972b). Haloperidol in AVMAN, N. and ARASIL, E. (1969). Spas­ leptiques. Rev. Neurol. (Paris), 114, 65-68. spasmodic torticollis. Lancet, 2, 234-235. modic torticollis due to a colloid cyst of the CHOPPY-JACOLIN, M., FERREY, G. and GILBERT, G.J. (1972c). Treatment of spas­ third ventricle. Acta Neurochir. (Wien), 21, DEMARIA, C. (1977). A psychometric modic torticollis. New Engl. J. Med., 286, 265-268. study of 34 patients afflicted with spasmodic 1161-1162. AYD, F.J. (1961). A survey of drug-induced torticollis. Acta Neurol, Scand., 55,483-492. GILBERT, G.J. (1977a). Familial spasmodic extrapyramidal reactions. J. Am. Med. COCKBURN, J.J. (1971). Spasmodic torti­ torticollis. Neurology, 27, 11-13. Assoc, 175, 1054-1060. collis: a psychogenic condition? J. Psycho- GILBERT, G.J. (1977b). Treatment questioned BARBEAU, A., MARS, H. and GILLO- somat. Res., 15, 471-477. in familial spasmodic torticollis. Reply from JOFFROY, L. (1971). Adverse clinical side COTTOM, D.G. and NEWMAN, C.G.H. the author. Neurology, 27, 900. effects of levodopa therapy. In Recent (1966). Dystonic reactions to phenothiazine GRINKER, R. R. and WALKER, A. E. (1933). Advances in Parkinson's Disease, Edited by derivatives. Arch. Dis. Child., 41, 551-553. The pathology of spasmodic torticollis with F.H. McDowell and C.H. Markham, pp a note on respiratory failure from anesthesia 203-237, F.A. Davis Co, Philadelphia. COUCH, J.R. (1976a). General discussion of drug-therapy in dystonia. Adv. Neurol., 14, in chronic encephalitis. J. Nerv. Ment. Dis., BARRETT, RE., YAHR, M.D. and DU- 417-422. 78, 630-637. VOISIN, R.C. (1970). Torsion dystonia and GUPTA, J.M. and LOVEJOY, F.H. (1967). spasmodic torticollis-results of treatment COUCH, J. R. (1976b). Dystonia and tremor in Acute phenothiazine toxicity in childhood: a with L-dopa. Neurology, 20, Suppl. 107-113. spasmodic torticollis. Adv. Neurol., 14, 245- 258. five-year survey. Pediatrics, 39, 771-774. BATT1STA, A.F., GOLDSTEIN, M., MIYA­ MOTO, T. and MATSUMOTO, Y. (1976). COUPER-SMARTT, J. (1973). Lithium in HARENKO, A. (1967). Retrocollis as an irre­ Effect of centrally acting drugs on experi­ spasmodic torticollis. Lancet, 2, 741-742. versible late complication of neuroleptic mental torticollis in monkeys. Adv. Neurol., CRITCHLEY, M. (1939). Spastic dysphonia medication. Acta Neurol. Scand. 43, Suppl. 14, 329-338. ("inspiratory speech"). Brain, 62, 96-103. 31: 145-146. BERNHARDT, A.J., HERSEN, M. and CROSSMAN, A.R. and SAMBROOK, M.A. HASSIN, G.B. (1939). Quinine and dystonia BARLOW, D. H. (1972). Measurement and (1978). Experimental torticollis in the musculorum deformans. J. Am. Med. modification of spasmodic torticollis: an monkey produced by unilateral 6-hydroxy- Assoc, 113, 12-14. experimental analysis. Behav. Therap., 3, dopamine brain lesions. Brain Res., 149, HASSLER, R. and DIEKMANN, G. (1970). 294-297. 498-502. Stereotactic treatment of different kinds of

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spasmodic torticollis. Confin. Neurol. 32, MARSDEN, CD. (1976). The problem of SHAW, K.M., HUNTER, K. R. and STERN, 135-143. adult-onset idiopathic torsion dystonia and G.M. (1972). Medical treatment of spas­ HERZ, E. and GLASER, G.H. (1949). Spas­ other isolated dyskinesias in adult life modic torticollis. Lancet, 1, 1399. modic torticollis. II. Clinical evaluation. (including blepharospasm, oromandibular S1GWALD, J., BOUTTIER, D., MME. Arch. Neurol. Psychiat. 61, 227-239. dystonia, dystonic writer's cramp, and tor­ CAILLE and GINESET. D. (1959). Deux ticollis or axial dystonia. Adv. Neurol. 14, cas de syndrome dystonique et dyskinetique HIRSCHMANN, J. and MAYER, K. (1964). 259-276. Zur Beeinflussung der Akinese und anderer cervico-cephalique (torticolis spasmodique, extrapyramidal-motorischer Storungen mit MATHEWS, W.B., BEASLEY, P., PARRY- retrocolis) transforme par le 2 bismethane L-Dopa (L-Dihydroxyphenylalanin). Deutsch. JONES, W. and GARLAND, G. (1978). sulfonate de dimethylsulfamido-3 [(m£thyl-4 Med. Wschr., 89, 1877-1880. Spasmodic torticollis: a combined clinical "piperazinyl-1") -3' propyl] -10 phenothia- study. J. Neurol. Neurosurg. Psychiat., 41, zine (7843RP). Rev. Neurol. (Paris), 100, JOHANSSON, B. and ROOS, B-E. (1974). 5- 485-492. 778-780. Hydroxyindoleacetic acid and homovanillic SIGWALD, J. and RAYMONDEAUD, C acid in cerebrospinal fluid of patients with MEARES, R. (1971). Natural history of spas­ (1970). Les mouvementsanormaux observed neurological diseases. Europ. Neurol., 11, modic torticollis and effect of surgery. au cours du traitement de la maladie de 37-45. Lancet, 2, 149-151. Parkinson par la L-dopa. Rev. Neurol. KJELLIN, KG. and STIBLER, H. (1975). MORI, K., FUJITA, Y., SHIMABUKURO, (Paris), 122, 103-112. Cerebrospinal fluid protein patterns in H., ITO, M. and HANDA, H. (1975). Some SWASH, M., ROBERTS, AH., ZAKKO, H. spasmodic torticollis. Europ. Neurol., 13, considerations for treatment of spasmodic and HEATHFIELD.K.W.G.(1972). Treat­ 461-475. torticollis. Clinical and experimental stu­ ment of involuntary movement disorders dies. Confin. Neurol. 37, 265-269. KOREIN, J. (1977). Treatment questioned in with tetrabenazine. J. Neurol. Neurosurg. familial spasmodic torticollis. Neurology, MYERSON, A. and LOMAN, J. (1942). Psychiat., 35, 186-191. 27, 899-900. Amphetamine sulfate in treatment of SWETT, C. (1975). Drug-induced dystonia. KREBS, M.E. (1939). Note sur le traitement spasmodic torticollis. Arch. Neurol. Psy­ Am. J. Psychiat., 132, 532-534. pratique dans un cas de torticolis spasmo- chiat., 48, 823-828. TARLOV, E. (1970). On the problem of dique. Rev. Neurol. (Paris), 71, 423-424. PAPESCHI, R., MOLINA-NEGRO, P., pathology of spasmodic torticollis in man. J. Neurol. Neurosurg. Psychiat., 33, 457-463. LAL, S., HOYTE, K.M., KIELY, M.E., SOURKES,T. L. and ERBA, G. (1972). The SOURKES, T.L., BAXTER, D.W., MIS- concentration of homovanillic acid and TOLOSA, E.S. (1978). Modification of tardive SALA, K. and ANDERMANN, F. (1979). 5-hydroxyindoleacetic acid in ventricular dyskinesia and spasmodic torticollis by Neuropharmacological investigation and and lumbar CSF. Neurology, 22,1151-1159. apomorphine. Arch. Neurol., 35, 459-462. treatment of spasmodic torticollis. Adv. PATTERON, R.M. and LITTLE, S.C (1943). TR1LLET, M., JOYEUX, O. and MASSON, Neurol, (in press). Spasmodic torticollis. 98, 571-599. R. (1977). Tiapride et mouvements anor- maux. Sem. H6p. (Paris), 53, 21-27. LATERRE, E.C. and FORTEMPS, E. (1975). PERNIKOFF, M. (1964). Treatment of acute Deanol in spontaneous and induced dyski­ and chronic muscle spasm with diazepam. TURNER, S.M., HERSEN, M. and AL- nesias. Lancet, 1, 1301. Clin. Med. 71, 699-705. FORD, H. (1974). Effects of massed prac­ tice and meprobamate on spasmodic torti­ LEES, A., SHAW, K.M. and STERN, G.M. PODVINSKY, F. (1969). Role of sensory and collis: an experimental analysis. Behav. (1976). Bromocriptine and spasmodic torti­ emotional inputs in mechanisms underlying Ther., 12, 259-260. involuntary motor activity. Modern con­ collis. Brit. Med. J., 1, 1343. URECHIA, CI. and MME RETEZEANU cepts of torticollis. 1. Electromyographic (1937). Parkinsonisme avec torticolis spas­ MARKH AM, C. H., CLARK, W. G. and WIN­ analysis. Activ. Nerv. Sup. 11, 11-29. TERS, W.D. (1963). Effect of alpha-methyl modique ou avec tics buccaux. Arch. dopa and reserpine in Huntington's chorea, POIRIER, L.J. (1960). Experimental and his­ Neurol. (Paris), 56, 491-494. Parkinson's disease and other movement tological study of midbrain dyskinesias. J. WEST, H.H. (1977). Treatment of spasmodic disorders. Life Sci., 9, 697-705. Neurophysiol., 23, 534-551. torticollis with amantadine: a double-blind MARSDEN, CD., TARSY, D. and BALD- POPPEN, J.L. and MARTINEZ-NIOCHET, study. Neurology, 27, 198-199. ESSARINI, R.J. (1975). Spontaneous and A. (1951). Spasmodic torticollis. Surg. Clin. WIMMER, A. (1929). Le spasme de torsion. drug-induced movement disorders in psy­ N. Amer., 31, 883-890. Rev. Neurol. (Paris), I, 904-915. chotic patients. In Psychiatric Aspects of PUTNAM, T.J., HERZ, E. and GLASER, W1NTHER, K. (1930). Tumeur du quatrieme Neurologic Disease, Edited by D. F. Benson G.H. (1949). Spasmodic torticollis. 111. ventricule, se manifestant seulement par une and D. Blumer,pp219-266,GruneandStrat- Surgical treatment. Arch. Neurol. Psychiat. deviation de la t£te. Acta Psychiat. Neurol., ton, New York. 61, 240-247. 5, 45-53.

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