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- Vol. 6 No. 4 NOVEMBER 1979 —427 Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.76, on 25 Sep 2021 at 17:19:45, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0317167100023830 THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES 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