Neurological features of Gilles Tourette's syndrome · Gilles de la Tourette's syndrome treated at the Payne Whitney Clinic of the NewYork Hospital-Cornell Medical Center were examined

Journal of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 1-9

Neurological features of Gilles de la Tourette'ssyndrome

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 syndromeand 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 inall 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. Thesefindings suggest that a neurological disorder underlies Tourette's syndrome, but they do not clarifyits nature.

Tics may be defined as brief purposeless move-ments of a body part which occur at randomintervals and cannot be suppressed for longperiods of time. Wilson (1927) believed they werepsychogenic in origin, while others have empha-sized developmental (Balthasar, 1957) or in-flammatory disorders (Creak and Guttman,1935) of the basal ganglia as possible causes.

Gilles de la Tourette (1885) described ninepatients with persistent multiple tics beginningin childhood Five of these patients also hadcoprolalia. Tourette linked tics with other raremotor and speech disorders, such as latah,myriachit, and 'jumping Frenchmen', andemphasized the chronic stable course suchpatients followed in adulthood.

Subsequent authors have differentiated 'mala-die des tics' from other involuntary motor dis-orders (Kelman, 1965; Chapel, 1970). Bothpsychiatric and neurological disorders havebeen invoked as causes of Tourette's syndromewithout conclusive evidence (Kelman, 1965;Challas, Chapel, and Jenkins, 1967; Corbett,Mathews, and Cornell, 1969; Morphew andSim, 1969).

Tourette's syndrome responds best to treat-ment with haloperidol (Chapel et al., 1964;Shapiro and Shapiro, 1968), a butyrophenonecompound which blocks dopamine receptors

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(Yeh, McNay, and Goldberg, 1969). It has beensuggested that a dopamine excess may underlieTourette's syndrome (Snyder, Taylor, Coyle, andMeyerhoff, 1970), but the actual anatomical orpathophysiological abnormality which mightcause Tourette's syndrome and be controlled byhaloperidol is still unknown.

Clinical neurological techniques have beenused by several authors in an effort to demon-strate a neurological deficit. Fernando (1967)reviewed the world's literature and noted nospecific findings, but found reports of abnormalelectroencephalograms (EEG) in 25%. Corbin,Goldstein, and Klass (1966) reviewed sevenpatients at the Mayo Clinic and again found nopertinent changes on examination but found sixpatients with rolandic sharp waves on EEG, fourwhile awake and two while asleep. Lucas (1970)described the EEGs of 12 patients, of whichseven were abnormal. Five showed diffuse mildto moderate slowing, one had posterior deltaactivity, and one showed bilateral spike andwave complexes.

Since subtle neurological abnormalities andclinical correlations may escape notice in a fewpatients, or in a group of patients examined byvarious physicians, we thought it worthwhile toreport the findings in a large series of patientswith Tourette's syndrome.

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

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METHODS

Twenty-two patients from a series of 34 patients withGilles de la Tourette's syndrome treated at thePayne Whitney Clinic of the New York Hospital-Cornell Medical Center were examined neuro-

logically. In addition, written reports of neurologicalexaminations of seven other patients in the serieswere reviewed. At the time of examination, 10 patientswere taking haloperidol, 2-8 mg/day and two were

taking benztropine. One other patient had takenhaloperidol and benztropine for three years, but was

examined after three weeks without medication. Acomplete medical history was taken with emphasison early life injury or illness, developmental ab-normalities, intercurrent illnesses, and medication.This information was obtained from patients andtheir relatives and supplemented by previousmedical records. A complete neurological examina-tion with special emphasis on motor phenomenawas performed, along with a general medicalexamination. Electroencephalograms were performedon 17 of the 22 patients using unipolar and bipolarmontages with 22 scalp leads. All patients were

hyperventilated during the recording. Five had bothawake and sleep EEGs and four had photic stimula-tion during EEG recording. Electromyographictracings from surface electrodes over muscles in-volved in tics were obtained concurrently with theEEG in one patient. Paper speed was increased from3 to 6 cm/sec during EEG-EMG recording tofacilitate detection of the start of activity.

HISTORY Data for all examined patients are sum-marized in Table 1.

Gestation and birth were normal in all but threeof the personally examined patients. One man hadrequired oxygen therapy and blood transfusionafter birth, presumably because of neonatal bloodincompatibility. Two boys' mothers had been pre-eclamptic while pregnant with them, but their birthand perinatal periods were normal. Labour, lasting10 hours, was induced in a third boy's primiparousmother at full gestation with no complication. Birthhistory was abnormal in three other patients amongthe total of 34, with two instances of prolongedlabour and one of pneumonitis. One reviewedpatient is a dizygotic twin whose sibling is notaffected by Tourette's syndrome. Birth weight ofexamined patients averaged 3-3 kg (7-2 lb.) andranged from 2-2 to 5*0 kg (4-8 to 11 1 lb.). Maternalage at birth averaged 27-8 years (19-36). Twelve ofthe 22 examined patients were first children, sevenwere second children, and three were third or lowerin order. Comparable figures for the 34 patients are

17, 11, and six.

Developmental milestones were reached normallyby all examined patients under the age of 18 years.Four older patients reported delayed sitting, walking,or talking; the reliability of their retrospective his-tories is questionable. Another three patients amongthe series of 34 had delayed milestones. Six patientsamong the 34 were late in toilet training and two ofthe boys who were examined were said to have been'clumsy' in early childhood.The patients were examined at an average age of

23 years (range 8-62). Ten of the 22 examinedpatients and six of the seven reviewed cases wereaged 15 years or less. Seventeen of the 22 examinedand six of the seven reviewed patients were males, apredominance also found in other series (Fernando,1967).Symptoms began at an average age of 7 years in

both examined and reviewed cases. Initial symptomsin examined patients consisted of frequent inappro-priate blinking or squinting in 10 patients, facial ticsin four, arm and shoulder movements in four, headbobbing in three, and barking in one. Progression oftics from face to proximal limb muscles and theappearance of vocal exclamations within a few yearswere typical.

Concomitant illnesses noted at the time ofexamination were cervical spondylosis, hiatal hernia,and transexualism. A woman had undergone bi-lateral cryothalamotomies with partial relief ofTourette's symptoms (Cooper, 1963), and a boy hadreceived insulin shock treatment and prochlor-phenazine for tics during his teens. One boy hadinfectious mononucleosis three months before theonset of his tics and a man gave an anecdotal historyof 'sleeping sickness' at 11 months of age.Handedness was inquired about routinely in the

interview. Five of the 22 personally examinedpatients were strongly left-handed and three othersconsidered themselves ambidextrous. Four othersamong the series of 34 patients were left-handed,giving a total of 12 patients among 34 (35W0) withGilles de la Tourette's syndrome who were ambi-dextrous or left-handed.

Family history disclosed two parents of patientswho had occasional facial tics, usually duringperiods of stress. A grandfather was said to have had'epilepsy', not further characterized. A patient's sondeveloped writhing hand movements lacking thecharacteristics of a tic at age 20 years. Two maternaluncles of a patient committed suicide and his motherwas periodically depressed. 'St. Vitus's dance',evidently consisting of chronic isolated chorea, led toyear long hospitalization of a patient's maternalgrandmother at the age of 16 years and his maternalaunt at the age of 9 years. Neither woman had eithera permanent movement disorder or valvular heart



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disease. The absence of tics in a twin of one patientis mentioned above.

Twenty-four of the 34 patients had at least partialAshkenazi Jewish ancestry. Antecedents of five otherswere Italian, three Anglo-Saxon, and one eachGerman and East European.

NEUROLOGICAL EXAMINATION Aside from tic pheno-mena, the standard neurological examination showedno striking changes. Cranial nerve functions wereentirely normal. The two oldest patients, 55 and 62years old, had mild distal symmetrical lower ex-tremity sensory loss.

Mild motor asymmetries were noticeable in 11 ofthe patients who were personally examined (Table 2).In 10 patients these were unilateral impairment ofrapid alternating movements, pronation or drift ofan outstretched extremity, increase in tone orreflexes or decreased associative movements on oneside, or decrease in tone and check on one side withataxia. These asymmetries occurred in patients whose

TABLE 2MOTOR ABNORMALITIES OTHER THAN TICS

IN TOURETTE'S SYNDROME

Patient Abnormality Handedness Medication

5 Decreased tone and check R Nonein left UE. Ataxia

6 Impaired alternating move- R Nonements and increasedDTRs in right LE

7 Impaired alternating and A Haloperidol,associative movements in benztropineright UE

8 Decreased right armswing R Haloperidol9 Left Babinski sign R Haloperidol10 Left sided weakness and A Prior insulin

incoordination shock andprochlorperazine

12 Decreased right armswing R Haloperidol13 Right UE pronation and L Haloperidol,

impaired alternating benztropinemovements

17 Left UE pronation and R Nonedrift

19 Increased tone and de- L Glutethemide,creased armswing on right propantheline

20 Impaired alternating move- R Nonements of left UE

A = ambidextrous.

age averaged 26 years and ranged from 11 to 62years. Four of the patients with motor asymmetrieswere taking haloperidol and one had received insulinshock therapy in the past. Unilateral motor changeswere not related to the site of tics.One other patient, a 16 year old boy (case 11),

was found to have a left Babinski sign and mildclumsiness on the left. Some of his tics were atypicalbecause of a dystonic component, though profusecoprolalia was documented. He developed episodesof 'rushing thoughts', paranoia, adversive headmovements to either side, and frequent tics afterthree years of haloperidol therapy. During an epi-sode observed in the hospital the patient was lethar-gic but oriented and capable of simple calculations.His vital signs, postural responses, and blood sugarwere normal. Such episodes usually lasted hours,though a short aura of 'far away feeling' sometimesoccurred without the episode itself. Skull radio-graphy and brain scan were normal. The EEG be-tween episodes showed bilateral frontotemporalsharp waves. A pneumoencephalogram was normal,though the CSF protein was 67 mg/100 ml. Theexact nature of this boy's episodes is unclear and he isbeing followed without specific treatment for them.Two boys, ages 8 and 14 years, exhibited short

attention span, clumsiness, and hyperactivity con-sistent with what has been termed 'minimal cerebraldysfunction'.

ABNORMAL MOVEMENTS Abnormal movements foundin Tourette's patients were generally proximal andrapid (Table 3). Facial grimaces occurred in 12

TABLE 3TICS OBSERVED IN TOURETTE SYNDROME

(22 PATIENTS)

Type of tic Patients(no.)

ProximalFacial 12Head shaking or thrusts 7Shoulder 13Thigh 3Jumps 1

DistalHands or feet 2

OthersChoreiform movements 7Athetosis 2Dystonia 1

examined and five reviewed patients. They wereusually associated with brief eye closure and shoulderelevation. Abrupt rotation of the head in one direc-tion was seen in four examined and two reviewedpatients. Another examined patient had rapid to andfro rotations of head on neck resembling a negativehead shake. Forward head thrusts were seen in twoexamined and one reviewed patient.

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Shoulder elevation or rapid 'shrugging' move-ments were present in 13 examined and two reviewedcases. These movements might be unilateral or bi-lateral and extended to ballistic abduction of one orboth upper extremities in three patients. Briefflexion-adduction movements of both thighs wereseen in three examined patients and sudden irregularjumps with windmill sweeps of the arms in oneother.

Distal motor abnormalities were not as marked oras common as proximal ones. Isolated tics ofhands orfeet were seen in two examined and one reviewedpatients. 'Wipingmovements' oftheupper extremitiesand 'toe curling' were described in two reviewedpatients. Distal choreiform movements, usually notedonly if specifically sought, were found in sevenexamined and two reviewed patients. In addition,athetosis was found in the right arm of the patientwho had had bilateral cryothalamotomies and inboth arms of a 15 year old boy taking haloperidoland benztropine. Dystonic inversion of either footand brief torticollis were seen in the 16 year old boydescribed in detail above. Torsion movements of thetrunk were seen in a motion picture of this patienttaken at age 13 before haloperidol had been started.Sudden patterned movements were also noted in a

few patients and they seemed to be related to pos-tural changes. One man briefly lapsed into a flexedposture during sustained muscular effort. A boyrepeatedly bent forward and flexed his arms into hisepigastrium and another boy suddenly struck hischest with closed fist of his right hand at irregularintervals. One reviewed patient was said to lapse intoa 'knee bend' posture. None of these patients wastaking haloperidol or other medication at the timesuch patterned movements were observed.

Haloperidol may have caused tremors that wereobserved in two of the examined patients. A 26 yearold woman taking haloperidol, 4 mg/day, andbenztropine had intermittent 2-4/sec resting tremorin her right thumb in addition to impaired rapidmovements and drift of the outstretched right arm.Mild bilateral intention tremor was found in an 8year old boy taking haloperidol, 5 mg/day. However,a 62 year old man who was taking no medicationsalso had left upper extremity sustention and intentiontremor in addition to impaired rapid movements.Three reviewed patients, aged 10, 15, and 38 yearsand taking no medication, were said to have tremorof outstretched hands.

VOCAL PHENOMENA Vocal phenomena were foundin all patients. Initially, grunts, coughs, or 'barks'were usually associated with tics. After a period oftime, usually several years, formed words becamepart of the vocal tic in 13 examined patients. Copro-

lalia supervened in 10 patients. Echolalia, theinvoluntary repetition of words uttered by others,was noted in seven patients. Coprolalia was recordedin two reviewed patients and one of these also hadecholalia.

Aside from coprolalia and echolalia, vocal utter-ances sometimes took fascinating forms. Twopatients exclaimed 'ow! wow! ow!'. Others inter-spersed hisses, spitting, and coughs. One boy in-appropriately accented words in mid-sentence.As with motor tics, stress intensified vocal

phenomena which could be suppressed voluntarilyfor minutes, or even hours in mild cases. Patientsexpressed a sense of relief upon gaining access toprivacy and 'allowing the words to come out'.An abnormal respiratory pattern was noted in a

62 year old man with tics and shouts since the age of6 years. Periodic tachypnoea and apnoea with rapidtransition from one to the other and an overall fre-quency of seven per minute occurred while he wasawake or drowsy. Tics usually began on the expira-tion of a deep breath. During sleep, regular respira-tions at 20-22/min were seen. Arterial blood gases,drawn with the patient awake, showed a mildrespiratory acidosis and 100%I oxygen saturation.

GENERAL EXAMINATION The general medical exami-nation disclosed no consistent abnormalities. Twopatients had soft non-radiating apical systolic cardiacmurmurs, another a pectus excavatum deformity,and another dependent pedal oedema.

ELECTROENCEPHALOGRAM Seventeen patients whohad neurological examinations also had an electro-encephalogram. Twelve of these EEGs were ab-normal (Table 4). Nine tracings showed paroxysmalfeatures consisting of bilateral sharp waves in eight,and left posterior sharp waves associated with leftparietal-temporal-occipital slow waves in one other.The bilateral sharp waves were posterior in fourtracings, diffuse in three, and frontotemporal in one.One of these patients had simultaneous EMGmonitoring of tics during his EEG and the timing ofhis occipital sharp waves was independent of motoractivity. Sharp waves in EEG's from the otherpatients also seemed to be independent of tics,though EMG confirmation was not obtained. Fourof these patients were taking haloperidol, 4 mg/day,and one who had undergone bilateral cryosurgerywas also taking amantadine, 300 mg/day. Oneother patient had bilateral sharp waves associatedwith tic movements.The remaining abnormalities consisted of diffuse

background disorganization and slowing in awaketracings of two patients, one of whom was takinghaloperidol 4 mg/day and benztropine. Five of the



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TABLE 4ELECTROENCEPHALOGRAPHIC FINDINGS IN

TOURETTE'S SYNDROME (17 PATIENTS)

Normal 5Sharp waves 9

Bilateral 8Left posterior I

Diffuse background disorganiza-tion and slowing 7Alone 2With bilateral sharp waves 5

tracings with paroxysmal activity also had back-ground disorganization.The provocative techniques of hyperventilation,

sleep, and photic stimulation did not change theEEG patterns significantly.

DISCUSSION

The examination of these 22 patients with Gillesde la Tourette's syndrome has disclosed threefactors of possible importance in understandingthe cause of this condition. These are a highprevalence of left-handedness, minor motorasymmetries, and electroencephalographic ab-normalities.A high prevalence of left-handedness (eight of

22 patients examined, or 36%, were left handedor ambidextrous) might be interpreted as evi-dence of left cerebral damage which might in turnbe due to the underlying abnormality inTourette's syndrome. Though Hecaen and deAjuriaguerra (1964) quote the frequency of left-handedness as 1 to 300% in various series, theycite the most likely frequency as between 5 and10%. Other factors to be considered are the pre-

dominance of males both among left-handedpeople and Tourette's patients and the tendencyof children to acquire firm hand preference onlyafter the first decade of life. Despite thesereservations, the frequency of left-handedness inthis series is high enough to warrant speculationon the relationship of early life brain injury toTourette's syndrome.The finding of minor motor asymmetries in

half the patients examined carefully may alsoindicate such a relationship. Similar findingshave been associated with the syndrome ofminimal cerebral dysfunction which someinvestigators link to birth trauma (Paine, 1962;

Prechtl and Stemmer, 1962; Anderson, 1963;Twitchell, LeCours, Rudel, and Teuber, 1966).Also three of the six patients with right-sidedmotor abnormalities were left-handed or ambi-dextrous. However, the somatic asymmetrywhich often accompanies early life hemispheraldamage was not found in our patients. Also, themotor findings were not seen in the youngestpatients. Moreover, lack of a control populationfor examination meant that determination ofmotor abnormality depended solely on theneurologist's clinical judgement. Most import-ant, the slight arm drift, pronation, increasedtone, and clumsiness found in those patientswere extremely subtle in comparison with theirobvious tics.

Electroencephalographic abnormalities werefound in 12 of the 17 Tourette patients who alsohad neurological examinations. This confirmsthe findings of other series (Ungher, Ciurea, andVolanschi, 1962; Field et al., 1966; Fernando,1967; Lucas, 1970), although our patientsshowed posterior abnormalities more often thanthe rolandic or parietal abnormalities describedby others. No specific or characteristic electro-encephalographic pattern was noted in patientswith the syndrome.The frequency of non-specific EEG abnormali-

ties in 'normal' populations has ranged from5-6% to 32% (Secunda and Finley, 1942; Corbinand Bickford, 1955, Hill, 1963), figures farexceeded by those of our patients (12 of 17 or700%). Clinically inapparent tics could be re-sponsible for the sharp wave abnormalities notedand we are undertaking a study with needleEMG electrodes and modified time constants toinvestigate this point. The background dis-organization found in seven of 17 records (41 %)cannot be attributed to tics. Haloperidol hasbeen found to increase either slow and sharp orfast activity in the scalp electroencephalogram(Itil, Gannon, Hsu, and Klingenberg, 1970) andsix of the patients with abnormal tracings weretaking this medication. However, these patients'abnormalities did not fall into any one categoryand two other patients taking haloperidol hadnormal records. Lucas (1970) found that halo-peridol did not change his patient's EEGssignificantly.Taken together, the high frequencies of left-

handedness, minor motor findings, and electro-

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encephalographic abnormalities suggest organicabnormality of the central nervous system as aconcomitant of Tourette's syndrome. This sug-gestion is further strengthened by the results ofpsychological tests of patients with Tourette'ssyndrome. Slight to moderate indices of organicdysfunction were present in 23 of 30 patients(770%) given WAIS or WISC, Bender Gestalt,and Rorschach tests (Shapiro, Shapiro, andClarkin, in preparation).The nature of the neurological pathophysi-

ology of Tourette's syndrome, if it exists, has notbeen ascertained by this study. Sudden patternedmovements of the face, trunk, or proximalextremities suggest hyperactivity of centralmotor mechanisms. Whether this is due toprimary irritability or removal of inhibition isunknown. Dopaminergic hyperactivity in thecorpus striatum has been postulated as thepharmacological mechanism for Tourette's syn-drome (Snyder et al., 1970; Messiha, Knopp,Vanecko, O'Brien, and Corson, 1971) because ofhaloperidol's suppression of tic symptoms andblockade of dopaminergic receptors, but thishypothesis has not yet been substantiated (DiGiacomo, Fahn, Glass, and Westlake, 1971).Vocal tics, especially coprolalia, have been citedas evidence for a psychological cause ofTourette'ssyndrome (Morphew and Sim, 1969), but forcedutterances and respiratory tics are well describedfollowing von Economo's encephalitis (Turnerand Critchley, 1925; Van Bogaert, 1934;Wohlfahrt, Ingvar, and Hellberg, 1961). Onlytwo of our patients had any historical suggestionof encephalitis (mononucleosis and 'sleepingsickness') and none showed ocular or extra-pyramidal signs which could not be attributed tomedication. Also, no patient had signs or symp-toms of rheumatic heart disease, which wouldsuggest Sydenham's chorea. (Creak and Gutt-mann, 1935; Aron et al., 1965). Thus, there is noevidence for an infectious or post-infectiouscause of Tourette's syndrome, though a sub-clinical or slow viral infection may have beenoverlooked.The consistent age and manner of onset of

Tourette's syndrome in our patients could beascribed to an inborn constitutional abnor-mality. The progression of tics from periocularto facial to proximal limbs to trunk is reminiscentof the course of heredofamilial tremor (Larson

and Sj"ogren, 1960). A patient with multiple ticsand acanthocytosis without serum lipid ab-normality has been described (Critchley, Betts,Nicholson, and Weatherall, 1970) but no othermetabolic abnormality has been associated withtics. The family histories of our patients revealedseveral interesting motor disorders ('St. Vitus'sdance', writhing hand movements) but no con-sistent pattern.

Because of the non-fatal course followed bypatients with tic syndromes, there are only twonecropsy reports of such patients in the litera-ture. One was normal (DeWulf and VanBogaert,1941) and the other reported subtle cellularchanges in the corpus striatum ('cynthohyper-plethora') attributed to developmental arrest(Balthasar, 1957). Neither showed changeswhich one could associate with early life cerebralinjury or infection.Though examination of our 22 patients with

Tourette's syndrome has disclosed subtle ab-normalities suggesting a neurological disorder,we doubt that similar studies will yield moresignificant information. Further clarification ofthe pathophysiology of Tourette's syndrome, andof related movement disorders, will require moresophisticated investigative techniques, especiallyinvestigation of the pharmacology of putativeneurotransmitters in patients with this perverseillness of Gilles de la Tourette.

Supported in part by the American Parkinson'sDisease Association (Dr. Sweet). We thank Dr.Henry Baird, St. Christopher's Hospital for Chil-dren, Philadelphia, for data and motion pictures onpatient no. 11.

REFERENCES

Anderson, W. W. (1963). The hyperkinetic child: a neuro-logical appraisal. Neurology (Minneap.), 13, 968-973.

Balthasar, K. (1957). Uber das anatomische Substrat dergeneralisierten Tic-Krankheit (maladie des tics, Gilles de laTourette): Entwicklungshemmung des corpus striatum.Archivfur Psychiatrie und Nervenkrankheiten, 195, 531-549.

Bogaert, I. van (1934). Ocular paroxysms and palilalia.Journal of Nervous and Mental Disease, 80, 48-61.

Challas, G., Chapel, J. L., and Jenkins, R. L. (1967).Tourette's disease: control of symptoms and its clinicalcourse. International Journal of Neuropsychiatry, 3, Suppl.1, S-95-S-109.

Chapel, J. L. (1970). Latah, myriachit, and jumpers revisited.New York State Journal of Medicine 70, 2201-2204.

Chapel, J. L., Brown, N., and Jenkins, R. L. (1964). Tourette'sdisease: symptomatic relief with haloperidol. AmericanJournal of Psychiatry, 121, 608-610.



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Corbett, J. A., Mathews, A. M., Connell, P. H., and Shapiro,D. A. (1969). Tics and Gilles de la Tourette's syndrome: afollow-up study and critical review. British Journal ofPsychiatry, 115, 1229-1241.

Corbin, H. P. F., and Bickford, R. G. (1955). Studies of theelectroencephalogram of normal children: comparison ofvisual and automatic frequency analyses, Electroencephalo-graphy and Clinical Neurophysiology, 7, 15-28.

Creak, M., and Guttmann, E. (1935). Chorea, tics and com-pulsive utterances. Journal of Mental Science, 81, 834-839.

Critchley, E. M. R., Betts, J. J., Nicholson, J. T., andWeatherall, D. J. (1970). Acanthocytosis, normolipo-proteinaemia and multiple tics. Postgraduate MedicalJournal, 46, 698-701.

DeWulf, A., and van Bogaert, L. (1941). Etudes anatomo-cliniques des syndr6mes hypercinetiques complexes, III.Une observation anatomo-clinique de maladie des tics(Gilles de la Tourette). Monatsschrift fur Psychiatrie undNeurologie, 104, 53-61.

DiGiacomo, J. N., Fahn, S., Glass, J. B., and Westlake, R. J.(1971). A case with Gilles de la Tourette's syndrome: re-current refractoriness to haloperidol, and unsuccessfultreatment with L-dopa. Journal of Nervous and MentalDisease, 152, 115-117.

Fernando, S. J. M. (1967). Gilles de la Tourette's syndrome:a report on four cases and a review of published casereports. British Journal of Psychiatry, 113, 607-617.

Field, J. R., Corbin, K. B., Goldstein, N. P., and Klass,D. W. (1966). Gilles de la Tourette's syndrome. Neurology(Minneap.), 16, 453-462.

Gilles de la Tourette, G. (1885). Etude sur une affectionnerveuse caracterisee par l'incoordination motriceaccompagnee d'echolalie et de coprolalie (jumping,latah,myriachit), Archives de Neurologie, 9, 19-42, and 158-200.

Hecaen, H., and de Ajuriaguerra, J. (1964). Left-Handed-ness: Manual Superiority and Cerebral Dominance. Gruneand Stratton: New York.

Hill, D. (1963). The EEG in psychiatry. Electroencephalo-graphy, 2nd edn., pp. 368-428. Edited by D. Hill andG. Parr. Macdonald: London.

Itil, T. M., Gannon, P., Hsu, W., and Klingenberg, H. (1970).Digital computer analyzed sleep and resting EEG duringhaloperidol treatment. American Journal ofPsychiatry, 127,462-471.

Kelman, D. H. (1965). Gilles de la Tourette's disease inchildren: a review of the literature. Jouirnal of ChildPsychology and Psychiatry, 6, 219-226.

Larssoin, T., and Sjogren, T. (1960). Essential tremor. ActaPsychiatrica et Neurologica Scandinavica, 36, Suppl. 144.

Lucas, A. R. (1970). Gilles de la Tourette's disease: Anoverview. New York State Journal of Medicine, 70, 2197-2200.

Messiha, F. S., Knopp, W., Vanecko, S., O'Brien, V., andCorson, S. A. (1971). Haloperidol therapy in Tourette'ssyndrome: neurophysiological, biochemical, and behav-ioral correlates, Life Sciences, Part 1, 10, 449-457.

Morphew, J. A., and Sim, M. (1969). Gilles de la Tourette'ssyndrome: a clinical and psychopathological study,British Journal of Medical Psychology, 42, 293-301.

Paine, R. S. (1962). Minimal chronic brain syndromes inchildren. Developmental Medicine and Child Neurology,4, 21-27.

Prechtl, H. F. R., and Stemmer, Ch. J. (1962). The chorei-form syndrome in children. Developmental Medicine andChild Neurology, 4, 119-127.

Secunda, L., and Finley, K. H. (1942). Electroencephalo-graphic studies in children presenting behavior disorders.New England Journal of Medicine, 226, 850-854.

Shapiro, A. K., and Shapiro, E. (1968). Treatment of Gillesde la Tourette's syndrome with haloperidol. British Journalof Psychiatry, 114, 345-350.

Shapiro, E., Shapiro, A. K., and Clarkin, I. Psychologicaltesting in Tourette's syndrome. (In preparation.)

Snyder, S. H., Taylor, K. M., Coyle, J. T., and Meyerhoff,J. L. (1970). The role of brain dopamine in behavioralregulation and the actions of psychotropic drugs. AmericanJournal of Psychiatry, 127, 199-207.

Turner, W. A., and Critchley, M. (1925). Respiratory dis-orders in epidemic encephalitis. Brain, 48, 72-104.

Twitchell, T. E., Le Cours, A.-R., Rudel, R. G., and Teuber,H.-L. (1966). Minimal cerebral dysfunction in children:motor deficits. Transactions of the American NeutrologicalAssociation, 91, 353-355.

Ungher, J., Ciurea, E., and Volanschi, D. (1962). EEGanalysis of motor neurosis in children (infantile tics).(Abstract.) Electroencephalography and Clinical Neuro-physiology, 14, 147.

Wilson, S. A. K. (1927). The tics and allied conditions.Journal of Neurology and Psychopathology, 8, 93-109.

Wohlfart, G., Ingvar, D. H., and Hellberg, A.-M. (1961).Compulsory shouting (Benedek's 'klazomania') associatedwith oculogyric spasms in chronic epidemic encephalitis.Acta Psychiatrica Scandinavica, 36, 369-377.

Yeh, B. K., McNay, J. L., and Goldberg, L. I. (1969).Attenuation of dopamine renal and mesenteric vaso-dilation by haloperidol: evidence for a specific dopaminereceptor. Journal of Pharmacology and ExperimnentalThlerapy, 168, 303-309.

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Neurological features of Gilles Tourette's syndrome · Gilles de la Tourette's syndrome treated at the Payne Whitney Clinic of the NewYork Hospital-Cornell Medical Center were examined