J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.1 on 1 February 1973. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 1-9

Neurological features of Gilles de la Tourette's syndrome

RICHARD D. SWEET, GAIL E. SOLOMON, HENRIETTE WAYNE, ELAINE SHAPIRO, AND ARTHUR K. SHAPIRO From the Departments of Neurology and Psychiatry, Cornell University Medical College, New York, New York 10021, U.S.A.

SUMMARY Clinical neurological examinations of 22 patients with Gilles de la Tourette's syndrome and written reports of examinations of seven other patients are reported. Half the personally exam- ined patients had minor motor asymmetries in addition to the typical motor and vocal tics found in all the patients. Thirty-six per cent of patients were left handed or ambidextrous. Electroencephalo- grams performed on 17 of the 22 patients showed non-specific abnormalities in 12 of them. These findings suggest that a neurological disorder underlies Tourette's syndrome, but they do not clarify its nature. Protected by copyright.

Tics may be defined as brief purposeless move- (Yeh, McNay, and Goldberg, 1969). It has been ments of a body part which occur at random suggested that a dopamine excess may underlie intervals and cannot be suppressed for long Tourette's syndrome (Snyder, Taylor, Coyle, and periods oftime. Wilson (1927) believed they were Meyerhoff, 1970), but the actual anatomical or psychogenic in origin, while others have empha- pathophysiological abnormality which might sized developmental (Balthasar, 1957) or in- cause Tourette's syndrome and be controlled by flammatory disorders (Creak and Guttman, haloperidol is still unknown. 1935) of the basal ganglia as possible causes. Clinical neurological techniques have been Gilles de la Tourette (1885) described nine used by several authors in an effort to demon- patients with persistent multiple tics beginning strate a neurological deficit. Fernando (1967) in childhood Five of these patients also had reviewed the world's literature and noted no coprolalia. Tourette linked tics with other rare specific findings, but found reports of abnormal motor and speech disorders, such as latah, electroencephalograms (EEG) in 25%. Corbin, myriachit, and 'jumping Frenchmen', and Goldstein, and Klass (1966) reviewed seven http://jnnp.bmj.com/ emphasized the chronic stable course such patients at the Mayo Clinic and again found no patients followed in adulthood. pertinent changes on examination but found six Subsequent authors have differentiated 'mala- patients with rolandic sharp waves on EEG, four die des tics' from other involuntary motor dis- while awake and two while asleep. Lucas (1970) orders (Kelman, 1965; Chapel, 1970). Both described the EEGs of 12 patients, of which psychiatric and neurological disorders have seven were abnormal. Five showed diffuse mild been invoked as causes of Tourette's syndrome to moderate one had delta slowing, posterior on October 1, 2021 by guest. without conclusive evidence (Kelman, 1965; activity, and one showed bilateral spike and Challas, Chapel, and Jenkins, 1967; Corbett, wave complexes. Mathews, and Cornell, 1969; Morphew and Since subtle neurological abnormalities and Sim, 1969). clinical correlations may escape notice in a few Tourette's syndrome responds best to treat- patients, or in a group of patients examined by ment with haloperidol (Chapel et al., 1964; various physicians, we thought it worthwhile to Shapiro and Shapiro, 1968), a butyrophenone report the findings in a large series of patients compound which blocks dopamine receptors with Tourette's syndrome. 1 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.1 on 1 February 1973. Downloaded from 2 Richard D. Sweet, Gail E. Solomon, Henriette Wayne, Elaine Shapiro, and Arthur K. Shapiro

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4 Richard D. Sweet, Gail E. Solomon, Henriette Wayne, Elaine Shapiro, and Arthur K. Shapiro

METHODS Developmental milestones were reached normally by all examined patients under the age of 18 years. Twenty-two patients from a series of 34 patients with Four older patients reported delayed sitting, walking, Gilles de la Tourette's syndrome treated at the or talking; the reliability of their retrospective his- Payne Whitney Clinic of the New York Hospital- tories is questionable. Another three patients among Cornell Medical Center were examined neuro- the series of 34 had delayed milestones. Six patients logically. In addition, written reports of neurological among the 34 were late in toilet training and two of examinations of seven other patients in the series the boys who were examined were said to have been were reviewed. At the time ofexamination, 10 patients 'clumsy' in early childhood. were taking haloperidol, 2-8 mg/day and two were The patients were examined at an average age of taking benztropine. One other patient had taken 23 years (range 8-62). Ten of the 22 examined haloperidol and benztropine for three years, but was patients and six of the seven reviewed cases were examined after three weeks without medication. A aged 15 years or less. Seventeen of the 22 examined complete medical history was taken with emphasis and six of the seven reviewed patients were males, a on early life injury or illness, developmental ab- predominance also found in other series (Fernando, normalities, intercurrent illnesses, and medication. 1967). This information was obtained from patients and Symptoms began at an average age of 7 years in their relatives and supplemented by previous both examined and reviewed cases. Initial symptoms medical records. A complete neurological examina- in examined patients consisted of frequent inappro- tion with special emphasis on motor phenomena priate blinking or squinting in 10 patients, facial tics was performed, along with a general medical in four, arm and shoulder movements in four, head examination. Electroencephalograms were performed bobbing in three, and barking in one. Progression of on 17 of the 22 patients using unipolar and bipolar tics from face to proximal limb muscles and theProtected by copyright. montages with 22 scalp leads. All patients were appearance of vocal exclamations within a few years hyperventilated during the recording. Five had both were typical. awake and sleep EEGs and four had photic stimula- Concomitant illnesses noted at the time of tion during EEG recording. Electromyographic examination were cervical spondylosis, hiatal hernia, tracings from surface electrodes over muscles in- and transexualism. A woman had undergone bi- volved in tics were obtained concurrently with the lateral cryothalamotomies with partial relief of EEG in one patient. Paper speed was increased from Tourette's symptoms (Cooper, 1963), and a boy had 3 to 6 cm/sec during EEG-EMG recording to received insulin shock treatment and prochlor- facilitate detection of the start of activity. phenazine for tics during his teens. One boy had infectious mononucleosis three months before the HISTORY Data for all examined patients are sum- onset of his tics and a man gave an anecdotal history marized in Table 1. of 'sleeping sickness' at 11 months of age. Gestation and birth were normal in all but three Handedness was inquired about routinely in the of the personally examined patients. One man had interview. Five of the 22 personally examined required oxygen therapy and blood transfusion patients were strongly left-handed and three others because of neonatal blood considered themselves ambidextrous. Four others after birth, presumably http://jnnp.bmj.com/ incompatibility. Two boys' mothers had been pre- among the series of 34 patients were left-handed, eclamptic while pregnant with them, but their birth giving a total of 12 patients among 34 (35W0) with and perinatal periods were normal. Labour, lasting Gilles de la Tourette's syndrome who were ambi- 10 hours, was induced in a third boy's primiparous dextrous or left-handed. mother at full gestation with no complication. Birth Family history disclosed two parents of patients history was abnormal in three other patients among who had occasional facial tics, usually during the total of 34, with two instances of prolonged periods of stress. A grandfather was said to have had one of One reviewed not further characterized. A patient's son labour and pneumonitis. 'epilepsy', on October 1, 2021 by guest. patient is a dizygotic twin whose sibling is not developed writhing hand movements lacking the affected by Tourette's syndrome. Birth weight of characteristics of a tic at age 20 years. Two maternal examined patients averaged 3-3 kg (7-2 lb.) and uncles of a patient committed suicide and his mother ranged from 2-2 to 5*0 kg (4-8 to 11 1 lb.). Maternal was periodically depressed. 'St. Vitus's dance', age at birth averaged 27-8 years (19-36). Twelve of evidently consisting of chronic isolated chorea, led to the 22 examined patients were first children, seven year long hospitalization of a patient's maternal were second children, and three were third or lower grandmother at the age of 16 years and his maternal in order. Comparable figures for the 34 patients are aunt at the age of 9 years. Neither woman had either 17, 11, and six. a permanent movement disorder or valvular heart J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.1 on 1 February 1973. Downloaded from

Neurological features of Gilles de la Tourette's syndrome 5 disease. The absence of tics in a twin of one patient was found to have a left Babinski sign and mild is mentioned above. clumsiness on the left. Some of his tics were atypical Twenty-four of the 34 patients had at least partial because of a dystonic component, though profuse Ashkenazi Jewish ancestry. Antecedents offive others coprolalia was documented. He developed episodes were Italian, three Anglo-Saxon, and one each of 'rushing thoughts', paranoia, adversive head German and East European. movements to either side, and frequent tics after three years of haloperidol therapy. During an epi- NEUROLOGICAL EXAMINATION Aside from tic pheno- sode observed in the hospital the patient was lethar- mena, the standard neurological examination showed gic but oriented and capable of simple calculations. no striking changes. Cranial nerve functions were His vital signs, postural responses, and blood sugar entirely normal. The two oldest patients, 55 and 62 were normal. Such episodes usually lasted hours, years old, had mild distal symmetrical lower ex- though a short aura of 'far away feeling' sometimes tremity sensory loss. occurred without the episode itself. Skull radio- Mild motor asymmetries were noticeable in 11 of graphy and brain scan were normal. The EEG be- the patients who were personally examined (Table 2). tween episodes showed bilateral frontotemporal In 10 patients these were unilateral impairment of sharp waves. A pneumoencephalogram was normal, rapid alternating movements, pronation or drift of though the CSF protein was 67 mg/100 ml. The an outstretched extremity, increase in tone or exact nature of this boy's episodes is unclear and he is reflexes or decreased associative movements on one being followed without specific treatment for them. side, or decrease in tone and check on one side with Two boys, ages 8 and 14 years, exhibited short ataxia. These asymmetries occurred in patients whose attention span, clumsiness, and hyperactivity con- sistent with what has been termed 'minimal cerebral

dysfunction'. Protected by copyright. TABLE 2 ABNORMAL MOVEMENTS Abnormal movements found MOTOR ABNORMALITIES OTHER THAN TICS in Tourette's patients were generally proximal and IN TOURETTE'S SYNDROME rapid (Table 3). Facial grimaces occurred in 12 Patient Abnormality Handedness Medication 5 Decreased tone and check R None TABLE in left UE. Ataxia 3 6 Impaired alternating move- R None TICS OBSERVED IN TOURETTE SYNDROME ments and increased (22 PATIENTS) DTRs in right LE 7 Impaired alternating and A Haloperidol, associative movements in benztropine Type of tic Patients right UE (no.) 8 Decreased right armswing R Haloperidol 9 Left Babinski sign R Haloperidol Proximal 10 Left sided weakness and A Prior insulin Facial 12 incoordination shock and Head shaking or thrusts 7 prochlorperazine Shoulder 13 12 Decreased right armswing R Haloperidol

Thigh 3 http://jnnp.bmj.com/ 13 Right UE pronation and L Haloperidol, Jumps 1 impaired alternating benztropine Distal movements Hands or feet 2 17 Left UE pronation and R None Others drift Choreiform movements 7 19 Increased tone and de- L Glutethemide, Athetosis 2 creased armswing on right propantheline Dystonia 1 20 Impaired alternating move- R None ments of left UE

A =

ambidextrous. on October 1, 2021 by guest. examined and five reviewed patients. They were usually associated with brief eye closure and shoulder age averaged 26 years and ranged from 11 to 62 elevation. Abrupt rotation of the head in one direc- years. Four of the patients with motor asymmetries tion was seen in four examined and two reviewed were taking haloperidol and one had received insulin patients. Another examined patient had rapid to and shock therapy in the past. Unilateral motor changes fro rotations of head on neck resembling a negative were not related to the site of tics. head shake. Forward head thrusts were seen in two One other patient, a 16 year old boy (case 11), examined and one reviewed patient. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.1 on 1 February 1973. Downloaded from

6 Richard D. Sweet, Gail E. Solomon, Henriette Wayne, Elaine Shapiro, and Arthur K. Shapiro

Shoulder elevation or rapid 'shrugging' move- lalia supervened in 10 patients. Echolalia, the ments were present in 13 examined and two reviewed involuntary repetition of words uttered by others, cases. These movements might be unilateral or bi- was noted in seven patients. Coprolalia was recorded lateral and extended to ballistic abduction of one or in two reviewed patients and one of these also had both upper extremities in three patients. Brief echolalia. flexion-adduction movements of both thighs were Aside from coprolalia and echolalia, vocal utter- seen in three examined patients and sudden irregular ances sometimes took fascinating forms. Two jumps with windmill sweeps of the arms in one patients exclaimed 'ow! wow! ow!'. Others inter- other. spersed hisses, spitting, and coughs. One boy in- Distal motor abnormalities were not as marked or appropriately accented words in mid-sentence. as common as proximal ones. Isolated tics ofhands or As with motor tics, stress intensified vocal feet were seen in two examined and one reviewed phenomena which could be suppressed voluntarily patients. 'Wipingmovements' oftheupper extremities for minutes, or even hours in mild cases. Patients and 'toe curling' were described in two reviewed expressed a sense of relief upon gaining access to patients. Distal choreiform movements, usually noted privacy and 'allowing the words to come out'. only if specifically sought, were found in seven An abnormal respiratory pattern was noted in a examined and two reviewed patients. In addition, 62 year old man with tics and shouts since the age of athetosis was found in the right arm of the patient 6 years. Periodic tachypnoea and apnoea with rapid who had had bilateral cryothalamotomies and in transition from one to the other and an overall fre- both arms of a 15 year old boy taking haloperidol quency of seven per minute occurred while he was and benztropine. Dystonic inversion of either foot awake or drowsy. Tics usually began on the expira- and brief torticollis were seen in the 16 year old boy tion of a deep breath. During sleep, regular respira- described in detail above. Torsion movements of the tions at 20-22/min were seen. Arterial blood gases, Protected by copyright. trunk were seen in a motion picture of this patient drawn with the patient awake, showed a mild taken at age 13 before haloperidol had been started. respiratory acidosis and 100%I oxygen saturation. Sudden patterned movements were also noted in a few patients and they seemed to be related to pos- GENERAL EXAMINATION The general medical exami- tural changes. One man briefly lapsed into a flexed nation disclosed no consistent abnormalities. Two posture during sustained muscular effort. A boy patients had soft non-radiating apical systolic cardiac repeatedly bent forward and flexed his arms into his murmurs, another a pectus excavatum deformity, epigastrium and another boy suddenly struck his and another dependent pedal oedema. chest with closed fist of his right hand at irregular intervals. One reviewed patient was said to lapse into ELECTROENCEPHALOGRAM Seventeen patients who a 'knee bend' posture. None of these patients was had neurological examinations also had an electro- taking haloperidol or other medication at the time encephalogram. Twelve of these EEGs were ab- such patterned movements were observed. normal (Table 4). Nine tracings showed paroxysmal Haloperidol may have caused tremors that were features consisting of bilateral sharp waves in eight, observed in two of the examined patients. A 26 year and left posterior sharp waves associated with left old woman taking haloperidol, 4 mg/day, and parietal-temporal-occipital slow waves in one other. benztropine had intermittent 2-4/sec resting tremor The bilateral sharp waves were posterior in four http://jnnp.bmj.com/ in her right thumb in addition to impaired rapid tracings, diffuse in three, and frontotemporal in one. movements and drift of the outstretched right arm. One of these patients had simultaneous EMG Mild bilateral intention tremor was found in an 8 monitoring of tics during his EEG and the timing of year old boy taking haloperidol, 5 mg/day. However, his occipital sharp waves was independent of motor a 62 year old man who was taking no medications activity. Sharp waves in EEG's from the other also had left upper extremity sustention and intention patients also seemed to be independent of tics, tremor in addition to impaired rapid movements. though EMG confirmation was not obtained. Four Three reviewed patients, aged 10, 15, and 38 years of these patients were taking haloperidol, 4 mg/day, on October 1, 2021 by guest. and taking no medication, were said to have tremor and one who had undergone bilateral cryosurgery of outstretched hands. was also taking amantadine, 300 mg/day. One other patient had bilateral sharp waves associated VOCAL PHENOMENA Vocal phenomena were found with tic movements. in all patients. Initially, grunts, coughs, or 'barks' The remaining abnormalities consisted of diffuse were usually associated with tics. After a period of background disorganization and slowing in awake time, usually several years, formed words became tracings of two patients, one of whom was taking part of the vocal tic in 13 examined patients. Copro- haloperidol 4 mg/day and benztropine. Five of the J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.1 on 1 February 1973. Downloaded from Neurological features of Gilles de la Tourette's syndrome 7

TABLE 4 Prechtl and Stemmer, 1962; Anderson, 1963; ELECTROENCEPHALOGRAPHIC FINDINGS IN Twitchell, LeCours, Rudel, and Teuber, 1966). TOURETTE'S SYNDROME (17 PATIENTS) Also three of the six patients with right-sided motor abnormalities were left-handed or ambi- Normal 5 Sharp waves 9 dextrous. However, the somatic asymmetry Bilateral 8 which often accompanies early life Left posterior I hemispheral Diffuse background disorganiza- damage was not found in our patients. Also, the tion and slowing 7 motor were not seen Alone 2 findings in the youngest With bilateral sharp waves 5 patients. Moreover, lack of a control population for examination meant that determination of motor abnormality depended solely on the neurologist's clinical judgement. Most import- tracings with paroxysmal activity also had back- ant, the slight arm drift, pronation, increased ground disorganization. tone, and clumsiness found in those patients The provocative techniques of hyperventilation, were extremely subtle in comparison with their sleep, and photic stimulation did not change the obvious tics. EEG patterns significantly. Electroencephalographic abnormalities were found in 12 of the 17 Tourette patients who also DISCUSSION had neurological examinations. This confirms the findings of other series (Ungher, Ciurea, and

The examination of these 22 patients with Gilles Volanschi, 1962; Field et al., 1966; Fernando, Protected by copyright. de la Tourette's syndrome has disclosed three 1967; Lucas, 1970), although our patients factors of possible importance in understanding showed posterior abnormalities more often than the cause of this condition. These are a high the rolandic or parietal abnormalities described prevalence of left-handedness, minor motor by others. No specific or characteristic electro- asymmetries, and electroencephalographic ab- encephalographic pattern was noted in patients normalities. with the syndrome. A high prevalence of left-handedness (eight of The frequency of non-specific EEG abnormali- 22 patients examined, or 36%, were left handed ties in 'normal' populations has ranged from or ambidextrous) might be interpreted as evi- 5-6% to 32% (Secunda and Finley, 1942; Corbin dence ofleft cerebral damage which might in turn and Bickford, 1955, Hill, 1963), figures far be due to the underlying abnormality in exceeded by those of our patients (12 of 17 or Tourette's syndrome. Though Hecaen and de 700%). Clinically inapparent tics could be re- Ajuriaguerra (1964) quote the frequency of left- sponsible for the sharp wave abnormalities noted handedness as 1 to 300% in various series, they and we are undertaking a study with needle cite the most likely frequency as between 5 and EMG electrodes and modified time constants to http://jnnp.bmj.com/ 10%. Other factors to be considered are the pre- investigate this point. The background dis- dominance of males both among left-handed organization found in seven of 17 records (41 %) people and Tourette's patients and the tendency cannot be attributed to tics. Haloperidol has of children to acquire firm hand preference only been found to increase either slow and sharp or after the first decade of life. Despite these fast activity in the scalp electroencephalogram reservations, the frequency of left-handedness in (Itil, Gannon, Hsu, and Klingenberg, 1970) and this series is high enough to warrant speculation six of the patients with abnormal tracings were on the relationship of early life brain injury to taking this medication. However, these patients' on October 1, 2021 by guest. Tourette's syndrome. abnormalities did not fall into any one category The finding of minor motor asymmetries in and two other patients taking haloperidol had half the patients examined carefully may also normal records. Lucas (1970) found that halo- indicate such a relationship. Similar findings peridol did not change his patient's EEGs have been associated with the syndrome of significantly. minimal cerebral dysfunction which some Taken together, the high frequencies of left- investigators link to birth trauma (Paine, 1962; handedness, minor motor findings, and electro- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.1 on 1 February 1973. Downloaded from

8 Richard D. Sweet, Gail E. Solomon, Henriette Wayne, Elaine Shapiro, and Arthur K. Shapiro encephalographic abnormalities suggest organic and Sj"ogren, 1960). A patient with multiple tics abnormality of the central nervous system as a and acanthocytosis without serum lipid ab- concomitant of Tourette's syndrome. This sug- normality has been described (Critchley, Betts, gestion is further strengthened by the results of Nicholson, and Weatherall, 1970) but no other psychological tests of patients with Tourette's metabolic abnormality has been associated with syndrome. Slight to moderate indices of organic tics. The family histories of our patients revealed dysfunction were present in 23 of 30 patients several interesting motor disorders ('St. Vitus's (770%) given WAIS or WISC, Bender Gestalt, dance', writhing hand movements) but no con- and Rorschach tests (Shapiro, Shapiro, and sistent pattern. Clarkin, in preparation). Because of the non-fatal course followed by The nature of the neurological pathophysi- patients with tic syndromes, there are only two ology of Tourette's syndrome, if it exists, has not necropsy reports of such patients in the litera- been ascertained by this study. Sudden patterned ture. One was normal (DeWulf and VanBogaert, movements of the face, trunk, or proximal 1941) and the other reported subtle cellular extremities suggest hyperactivity of central changes in the corpus striatum ('cynthohyper- motor mechanisms. Whether this is due to plethora') attributed to developmental arrest primary irritability or removal of inhibition is (Balthasar, 1957). Neither showed changes unknown. Dopaminergic hyperactivity in the which one could associate with early life cerebral corpus striatum has been postulated as the injury or infection. pharmacological mechanism for Tourette's syn- Though examination of our 22 patients with drome (Snyder et al., 1970; Messiha, Knopp, Tourette's syndrome has disclosed subtle ab-Protected by copyright. Vanecko, O'Brien, and Corson, 1971) because of normalities suggesting a neurological disorder, haloperidol's suppression of tic symptoms and we doubt that similar studies will yield more blockade of dopaminergic receptors, but this significant information. Further clarification of hypothesis has not yet been substantiated (Di the pathophysiology ofTourette's syndrome, and Giacomo, Fahn, Glass, and Westlake, 1971). of related movement disorders, will require more Vocal tics, especially coprolalia, have been cited sophisticated investigative techniques, especially as evidence for a psychological cause ofTourette's investigation of the pharmacology of putative syndrome (Morphew and Sim, 1969), but forced neurotransmitters in patients with this perverse utterances and respiratory tics are well described illness of Gilles de la Tourette. following von Economo's encephalitis (Turner and Critchley, 1925; Van Bogaert, 1934; Supported in part by the American Parkinson's Wohlfahrt, Ingvar, and Hellberg, 1961). Only Disease Association (Dr. Sweet). We thank Dr. two of our patients had any historical suggestion Henry Baird, St. Christopher's Hospital for Chil- of encephalitis (mononucleosis and 'sleeping dren, Philadelphia, for data and motion pictures on no. 11. sickness') and none showed ocular or extra- patient http://jnnp.bmj.com/ pyramidal signs which could not be attributed to medication. Also, no patient had signs or symp- REFERENCES toms of rheumatic heart disease, which would Anderson, W. W. (1963). The hyperkinetic child: a neuro- suggest Sydenham's chorea. (Creak and Gutt- logical appraisal. Neurology (Minneap.), 13, 968-973. Aron et Thus, there is no Balthasar, K. (1957). Uber das anatomische Substrat der mann, 1935; al., 1965). generalisierten Tic-Krankheit (maladie des tics, Gilles de la evidence for an infectious or post-infectious Tourette): Entwicklungshemmung des corpus striatum. cause of Tourette's syndrome, though a sub- ArchivfurPsychiatrie und Nervenkrankheiten, 195, 531-549. Bogaert, I. van (1934). Ocular paroxysms and palilalia. on October 1, 2021 by guest. clinical or slow viral infection may have been Journal of Nervous and Mental Disease, 80, 48-61. overlooked. Challas, G., Chapel, J. L., and Jenkins, R. L. (1967). The consistent age and manner of onset of Tourette's disease: control of symptoms and its clinical course. International Journal of Neuropsychiatry, 3, Suppl. Tourette's syndrome in our patients could be 1, S-95-S-109. ascribed to an inborn constitutional abnor- Chapel, J. L. (1970). Latah, myriachit, and jumpers revisited. mality. The progression of tics from periocular New York State Journal of Medicine 70, 2201-2204. Chapel, J. L., Brown, N., and Jenkins, R. L. (1964). Tourette's to facial to proximal limbs to trunk is reminiscent disease: symptomatic relief with haloperidol. American of the course of heredofamilial tremor (Larson Journal ofPsychiatry, 121, 608-610. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.36.1.1 on 1 February 1973. 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