Dopamine D2 Receptor Imaging with Iodine-123-Iodobenzamide SPECT in Idiopathic Rotational Torticollis

Johannes Hierholzer, Michael Cordes, Ludwig Schelosky, Wolf Richter, Uwe Keske, Stephan Venz, Wolfhard Senunler, Werner Poewe and Roland Felix

Strahlenkiinik unci Neumlogirche KlinilÃ§Unive,@ritatskJiniIasmRudolf Virchow, Freie Universi:Ã¤t,Berlin and Institut fÃ¼r Diagnostikforschung; Berlin@Germany

may show rotational torticollis, laterocollis, retrocollis or The cause of idiopathic rotational torticoibs (tAT) is not corn combinations thereof (Table 1). According to the ad hoc pI@ understoodto date. However,basalgangbaare believed committee of the Dystonia Medical Research Fondation, to be involved in the pathophysiologyof IRT. To elucidatethis dystonia is classified by the age of onset, cause and body disorderfurther, the value ofiodobenzamide (IBZM) SPECT was distribution of the abnormal movement (Table 1). The cx studied for the evaluation of striatal dopamine D2 receptors in clusion of symptomatic dystoniajustifles the nominationof these patients.M@hods: StriataldopamineD2 receptordensity idiopathic focal dystonia (IFD) and, in case of head rota was assessed in 10 patientswith IRT using 1@I-IBZMSPECT. Theimageswereinterpretedbya nudearmedicinephysician tion, idiopathicrotationaltorticollis (IRT). initiallyto determineIBZMbindingwithinthe sthatumandthe The precise pathophysiology underlying idiopathic cerebellumand,secondly,intersthatalIBZMbinding.Theresuits adult-onset dystonia remains unclear. CF and MRI are werecorrelatedwiththedir@calparametersof the patentsand unable to detect consistent structuralchanges in patients compared w@i the results obtained from normal controls. with IFD (2), and postmortem examinations have not dem Results: No differencewasfoundin average,specificstiiatal onstrated consistent abnormalities in these patients (3). IBZMbinding(basalganglia/cerebellumratio)betweenpatients Focal lesions within the basal ganglia produce typical dys and controls. However, interstriatal analysis of IBZM binding tonia in patients with symptomatic dystonia; therefore, revealed a significantlyhigher binding in the striatum contralat eralto the directionof the torffcollis(p = 0.026,by chi-square dystonia is attributed to abnormal basal ganglia function test).ConclusIon:It wasconcludedthatthe striataldopamine (4). PET and SPECT provide the opportunity to assess D2receptorstatusisalteredinpatientswithIRT. functional abnormalities of the dopaminergic system of patients with idiopathic dystonia in vivo (5,6). Bun et al. Key Words: iodobenzamide;dopaminereceptor dystonia,@(7) found a positive correlation betweenthe striatal dopa @idiopath@crotationaltorticollis;IBZM SPECT mine D2 receptor density and the severity of the movement J NucIMed1994;35:1921-lW disorder in patients with tardive dyskinesia in whom dys tomais believedto be dueto neurolepticmedication.PET studies provide evidence of metabolic abnormalitiesin the basal ganglia in idiopathic dystorna In IRT, a breakdown ystoma is a syndrome characterized by sustained in the normal relationship of glucose metabolism between muscle contractions which frequently cause twisting and the thalamus and the basal gangliawas found (2). It was repetitive movements of the relative part of the body or postulated that this uncoupling might be related to dysfunc abnormalpostures (1). Prolongedabnormalcocontractions tion in thalamostriateor pallidothalamicprojections. of agonistandantagonistmuscleswithadditionalrecruit Crossman and Sambrock (8) induced torticollis spasmo mentof distantmusclescharacterizedystonianeurophys dicus in the monkey by injectinghydroxydopamineintothe iologically. This patterndistinguishes dystonia from other striatum. In this experiment, it was observed that the rel movement disorders. Most cases belong to the group of atively hyperactive (normal) striatum drives the head to the adult-onset idiopathic focal dystonia. Within this group, weaker contralateral side. All these data support the hy cervical dystonia (CD) is one of the most prevalent types. pothesis that the basal ganglia are involved in the patho Dependingon the type of head deviation, patientswith CD physiology of CD. Few data on the postsynaptic dopamine D2 receptor system in patients with CD have been published (9â€”11). In ReceivedMar.25, 1994;re@sionacceptedSept 7, 1994. a recent study, Leenders et al. (12) found an asymmetric For correspondenceor re@ cor*@ Johannes Hierhoizer,MD,StraHen kilnikundPolildink,Unlversit@sldlniwmRudoltVirchow,FreleUnlversllÃ¡tBerlin, bindingof â€œC-N-methylspiperoneto striatal D2 receptors @â€” PWz1,13353Berlin,Genneny. in a series of six patientswith focal dystonia (predominant

IBZMSPECTin IRTâ€¢Hierhoizerat al. 1921 TABLE I MATERIAI@SAND METHODS Classificationof Dystonia (1) Patients and Controls Cause Idiopathic Tenpatients(sevenmaleandthreefemale)who presentedto S-ic the Movement Disorder Clinic of the Departmentof Neurology, Famlilal UniversitÃ¤tsklinikum Rudolf Virchow with IRT were included in Symptomatic this study. The ages ranged from 32 to 59 yr (mean 43.8 yr, s.d. Ageof onset Chidhood (0-12 yr) 11.3yr). Nine patients had isolated IRT. One patient (P5)had Moisscent(13-20yr) Aduft(>2Oyr) additionalgraphospasmipsilateralto the IRT. DIstrIbution Focal All patients underwentdetailed neurologic examinationsby a Se@ senior neurologist (L.S.). The diagnoses were made on the basis Multifocal of clinical findings and polyelectromyographicresults. None of Gene@ed the patients had any other neurologicdisorder. Hemidystonia In allpatients,structurallesionswithinthebasalgangliahad Clinicalvariantsof Cissnictorsion beenexcludedby MRI.ThedetailsaregiveninTable2. Idiopathicform Eightappropriatecontrolsubjects(fivemaleandthreefemale), Paradoxic age range from 42 to 91 yr (mean 57.6 yr. s.d. 18.0 yr) were Myodonic studied. Statistically, the mean age of patients and controls was DIUrnal notsignificantlydifferent(p = 0.06).Noneof thecontrolsubjects Dopa-responsive had neuropsychiatricabnormalitiesor a family history of move mentdisorders.Onecontrol(C1)hadsufferedacorticalinfarction in the left parietal lobe 1 yr ago. ly rotational torticollis). A trend was found of higher stri All patients and controls were not receiving pharmacologic atal tracer uptake in the hemisphere contralateral to the therapy for at least 1 wk prior to SPECF. direction of head rotation. The examinationof patientsandhealthyvolunteerswas ap proved by the local institutional authorities ofthe Rudolf Virchow Iodine-123-IBZM has been shown to bind to dopamine MedicalCenter. Informedconsentwas obtainedfromeach sub D2 receptors with high affinityand specificity (5) and has ject. been used in several human studies to evaluate the regional cerebral dopamine D2 receptor density in men using RadIOtraCer SPECT (13â€”19). Indium-123-IBZM(S-(â€”)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2- To establish whether the postsynaptic dopaminergic hydroxy-3-kxio-6-methoxybenzamide, DuponVCygne, Eindhoven, functionis involvedin the pathophysiologyof IRT, â€˜DI TheNetherlands),was labeledby a kitproceduredevekpedby IBZM SPECF was performed in 10 patients with this dys Kung et al. (20). The chemical purity was more than 98%, and a tonic disorder. concentrationof â€˜@Iof less than 0.5%was found. The specific

TABLE 2 PatientandControlDataandResults

Subject1)P1M32ATno.SexAgeSymptomsIBZM BG/CBIBZMBG@BG@MRIi@% (SeeEquation .620.93Unremarkabie8.4P2M48RTtotheIght1 .760.98Unremarkable2.6P3M54RTtotheIght1 .540.91Unremarkable11.8P4M35RTtotheleft1 .540.93Unremarkabie9.2PSM33RTtotheright1 .00UnremarkaHe0.8P6F59RTtOtheIOft1.671.06PeriVentrIcUIaIWML8.1P7M56ATto therIght .571 graphospasm1

.01Unremarkable0.7P8F34AT to theleft1 .661 .710.94Unremarkable6.8p9F34ATto theright1 .01Unremarkable0.7p10M55ATto the left1 .731 .06Unremarkable7.8ClM55Acuteto theleft1 .001 [email protected] visionlossI .651 .02Cortical WML3.0c3M42CervIcal .631 .02Perlventricular .01Unremarkable0.8C4M42LDH1 myelopathy1 .581 .530.97Unremarkable3.4C5M80Lumbago1 atrophy2.4C6F50Lumbago1 .591 .03Pedventrlcular WML mild .640.97Unremarkable3.0C7M51Lumbago1.580.97Unremarkable4.0C8M50LDH1 .00Unremarkable0.0BG/CB .411

@ mdex ofspecificstriatalIBZMbinding, RT =rotationaltorticollis, WH =lumbar diskhemlation,WML= whitematterlesion.

1922 TheJournalofNudearMedicineâ€¢Vol.35â€¢No.12â€¢December1994 activity of the radiotracer was 2.4 x 10@Ci/mmole (5). Because of thehighSpecificityto dopamineD2receptors,theaccumulationof IBZM-gradingClinical the tracerin the striatumis dominatedby D2 receptorbindingand can be used to demonstrate the distribution of these receptors in vivo.

SPECTStudy gradingâ€”.@--1+10-1212@::@!.0320008x2-teSt@ An oral dose (300 mg) of sodium perchiorate was given to each subject1hrpriorto the studyto protectthe thyroidglandfromthe uptake of free iodine. After accurate positioning of the patient withtheheadinthecenterofrotation,thecamerarotatedaround to reduce the radius of rotation to a minimum. Positioning of pâ€”O.026 patients with rotating torticollis represented a special challenge; FIGURE1. Correlationoflntersfrlatal1@I-IBZMbindInganddi therefore a special effort was made to keep the head in a stable rectionof headrotationin patientswithIRTandin controls.Chi position. The headwas fixedwith a tape bandduringacquisition. squaretestprovesstatIsticalsignificance(p = 0.026).Clinicalgrad Correctionfor head tiltingwas possibleby the reconstruction ing:gradeâ€”1=headrotatIontotheleft,grade+1=headrotation algorithm (discussed later). A dose of 111 to 185 MBq (3â€”5mCi) of totheright,grade0 = controlsubjects.Gradingof IBZMSPECT: sterile, pyrogene-free â€˜@I-IBZMwas injected as a bolus into an gradeâ€”1= striatalIBZMbindIngrIght> left(> 4.8%),grade+1 = antecubital vein. SPECT studies were conducted with a single strlatalIBZMbindingleft> rIght(> 4.8%),grade0 = striatalIBZM head gamma camera connected to a dedicated computer system bindingrIght= left. anda low-energy,high-resolution,parallel-holecollimator(APC 3,Elscint).During360Â°rotation,60frameswereacquiredona64 x 64 matrix over approximately 60 mis. The timing for SPECT striatum (22). The size and position ofthe ROIs was kept the same was determinedfrom the in vivo kinetic data reported by this forallsubjects;allareasweredrawnby thesamereader(J.H.). group,whichshowedthat120-mmpostinjectionspecificstriatal Thereaderwasblindedtoanyclinicalinformationconcerningthe bindingof IBZM is on a high steady-state level (18). Therefore, subjects under investigation. For quantification, the concentration the tomographicacquisitionwas started 120 mm postinjectionin of the traceruptakewas calculatedby dividingthe meantracer all subjects. After normalizationfor inhomogeneity,the center of uptakein the striatumby the uptakein the cerebellum(basal rotationandphysicaldecayofthetracer,thedatawererearranged ganglia/cerebdllum ratio [BG/CB ratio]). Assuming that nonspe as transverse slices through a standard filtered back projection cific binding, affinityand access to the receptor are stable, the algorithm. Attenuation correction was not applied to the data BG/CB can be considered a reliableindex of striatalD2 receptor because no algorithm corrects adequately for heterogeneous tis density (23@24). sue-bone-airabsorption,especiallyat thelevelofthe nasopharynx Inaddition,interstriatalratios(i@%)werecalculatedaccording and the ears. to Equation1 (28): A four-step algorithm (MSCBREOB4X, Medisoft, Witten, Germany)was appliedto correctforabnormalheadpositionbe (BGT15hS/CB- BG1@@/CBx 200 L@%= cause head tilting is common in patients with torticollis. First, (BOrigh@/CB+ @Ieft/@) transverse slices (perpendicular to the detector ring) were recon structed with the optionto correct the slice orientationfor rota To transformnumericaldataintocategoricaldata,a clinical tion. Second,on the basis of these images,the reconstruction anda scintigraphicgradingwas performedaccordingto the fol algorithm generates a coronal slice (thickness 4 pixels) that allows lowingcriteria: grade +1 was assignedto head rotation to the theviewerto correcttheimagesincaseof atiltedpositionof the right, grade â€”1 to head rotation to the left and grade 0 to controls. patient'sheadandtoestablishavertical(paraaxial)planeperpen On scintigraphic studies, grade â€”1 was assigned to subjects with dicular to the long axis of the head. Third, on the basis of these 30 a significantlyhigherIBZMbindingin the rightstriatumcompared paraaxialslices, a midsagittalslice (thickness4 pixels)was gen with the left striatum. Grade + 1 was assigned to a higher binding crated to define the orbitomeatal line (OM line) in visual compar intheleftstriatum,andgrade0wasassignedtosymmetricstriatal ison to the MRI scans Fourth, finally, 15 slices (thickness IBZM binding (Fig. 1). 2 pixels = 8.4 mm) parallel to the OM line and, therefore, ana Theresultsobtainedwerethencorrelatedwithclinicalfindings. tomically identically oriented to the MM scans, were generated. MRI Study From these 15slices(thickness2 pixels= 8.4mm),two adjacent In all patients,MRIof the brainwas performedon a 1.5-T slices with the highest striatal uptake were selected in visual SiemensMagnetom,Erlangen,Germany;transversespin-echo, accordancewiththe identicallyorientedTi-weightedMRIscans. Ti-, T2-andproton-density-weightedimagesparallelto theOM Two slices within the cerebellum were selected and summed to line were acquired.Evaluationwas done with regard to lesions one slice for quantitativeanalysis.The cerebellarslices were withinthebasalgangliaandthe cerebellum(referenceregion)and automaticallyselectedby thecomputerprogramat iOmmabove regional or global brain atrophy. and parallel to the OM line. Concomitantly, two irregular regions of interest(ROIs)weredefinedfromSPEC!'imagesandfurther Data Analysis checkedbycomparisonwithTi-weightedMRIscansaidedbythe Two-tailed Student's t-test for unpaired samples was applied to humanbrainatlasproposedby Talairachet al. (21).Considering comparethetwogroupsunderinvestigationandtoevaluateasym the addedslice thicknessof 168 mm, the totalvolumeof the metricstriatalIBZMbindingin patientswith IRT. Datawere striatalRO! selected for quantificationwas approximately9 mL transformedintocategoricalgradingsaccordingto preestablished This volume corresponds to the neuroanatomic volume of the criteria;thechi-squaretestwasperformedtoevaluatewhetherthe

IBZMSPECTin IRTâ€¢Hierhoizerat al. 1923 @ @;

KLINIKUN RWOLF VIRCHOW 1.8 123â€”I-IBZMâ€”SPECT 0 p=o.11 0 0 @ 1.7 0 @ F@BASALGAHGL1@ 9 !. @ 0 :@C 1.6 0 C :@ 0 !N 0 0

1 2

â€”- CEREBELLUM Diagnoses(1=torticollis,2 =controls) FIGURE3@SpecificsthatalIBZMbinding(meanBG/CBratios)in patientswlthIRTandIncontrols(singleresults,0, andmeanvalues, FiGURE 2 Resultsof â€˜@l-1BZMSPECTin ControlC6. Trans â€¢1Â±s.d.). verse sliceswithROIsat the levelofthe basalgangila(top)and at thelevelofthe cerebelum(bottom).Highsymmetrict*dng of IBZM in the stilatum.Lowunspecifictrecerb@dngin the cerebellum. Patients BGICBratio = 1.64, @%= 3. Images are nOrmaliZedto the total injecteddose.ThesamecolorscaleIsappliedasin Figure4. In patients with IRT, the highest dopamine D2 receptor binding of â€˜@I-IBZMwas found within the basal ganglia. The frontal, temporal and cerebella activity were signifi cantly lower, reflecting predominantly nonspecific fixation two-parameter asymmetric binding and affected hemisphere were correlated.Thecorrelationofthesubject'sageandthedurationor KIINIKUM RI.U0LF@ VIRCHOL4 severity of IRT and IBZM binding was tested by linear-regression 123â€”I-IBZMâ€”SPECT analysis.For alltests, statisticalsignificancewas assumedat p < 0.05. Radiation Exposure Whole-body radiation exposure at an injected dose of lii to 1 185MBq â€˜@I-IBZMhasbeencalculatedto be i.8 to 3.0mSv, .â€”â€” BASAL GANGLIA basedon thebiodistributionascertainedby Kunget al. (20)and the ICRP 26 (38).

RESULTS The specific dopamineD2 receptorbindingof â€˜@I-IBZM in the striatumcompared with a reference region of non dopaminergic brain tissue (cerebellum) is expressed as a ratio and is listed for each individualin Table 2.

Control Subjects C In all control subjects, the highest uptake of â€˜@I-IBZM was found within the basal ganglia. Frontal, temporal and cerebellar activity was significantly lower, reflecting pre iiâ€”CEREBELLUM dominantlynonspecific bindingof the radiotracer(Fig. 2). @ The mean BG/CB ratio in controls was i.59 (s.d. = 0.05). FIGURE4. @. . .__.. @._@. .... _ent PlO,withthe No correlation of striatal IBZM binding with age was headrotatedto the left.Transversesliceswith ROIsat the levelof found (r = 0.20, p = 0.64). The mean interstriataldiffer the basalganglia(top)and at the levelof the cerebellum(bottom). H@herblndkigof IBZMinthe rIghtstilatumcomparedwIththe left ence (see Equation i) of IBZMbinding @%in controlswas side.Lowunspeciflctiacerbkdng Inthecerebellum.BG/CBratio= 2.4%(s.d. = i.4%). The rangeof normalinterstriatalvan 1.60, @%= 7.8.ImagesarenormalIzedtothetotalinjeoteddose. ation was defined as 0% to 4.8% (mean Â±2 s.d.). The samecolorscaleis appliedas in Figure2.

I924 TheJoumalof NuclearMedicsneâ€¢Vol. 35. No. 12. December1994 0 lidal activity. Foltz et al. (26) in the late i950s produced ipsiversive head rotation by making large lesions in the mesencephalic tegmentum in nonhuman primates. Cross

D 0 man and Sambrock (8) showed that selective lesions in the @ 0 dopaminergic pathway induced ipsiversive rotation of the @ I head in monkeys. This phenomenon is abolished by low dose apomorphine and exacerbated by amphetamine; high dose apomorphineproduced contraversive turning. How ever, the significance and the validity of animal 4 0 experiments has been questioned because an interspecies 0 0 0 variationmightbe responsible for differentbrainstemcon trol mechanisms of posture (27). PET studies of the re gional glucose metabolism in IRT did not completely cx plain the complex pathophysiology in humans (28). From recent work, there is some evidence that the

O@sgnos@(1â€”tor8co5s.2â€”convols) dopaminergic system is involved in the pathophysiology of FiGURE5. lnterstsiataldifferenceon1@l-IBZMbIndIngand @% IRT (3,1Z28). In this study, @I-IBZMSPECFwas used to (seeEquation1)in patientswIthIRTand in controls(singleresults, evaluate the dopamine D2 receptor density in patients with 0, andmeanvalues,S, Â±s.d.). IRT and in controls. It has been demonstrated that BG/CB ratios of the tracer binding positively correlates with the striatal D2 receptor density (B@(23,29). This index has of the radiotracer.The mean BG/CB ratiowas i.64 (s.d. = been shown to be independentof blood flow undersecular 0.08) and was not significantly different from that of the equilibrium,as demonstratedby previous PET studies us controls studied (p = OJi, Fig. 3). ing â€œC-raclopride(30). No correlation was found between the IBZM binding In this study, in patients with IRT the average specific and age (r = 0.03, p = 0.95) or the durationof IRT (r = striatal dopamine D2 receptor binding was not significantly 0.37. p = 0.30). The mean interstriatal difference (see different from the control group. However, patients exhib Equation i) of IBZM bindingA%was 5.7% (s.d. = 4.i%) ited a more asymmetric binding of the radioligandto the andwas significantlyhigherthanin the controls (p = 0.044) receptor compared with controls. In 5 of iO patients, a (Figs. 4 and 5). higher receptor binding was found in the striatum con When the asymmetric striatal IBZM binding was cone tralateralto the direction of head rotation. In one patient, lated with the direction of heat rotation, according to the however, an inverse binding characteristicwas found. In predefined clinical grading system, in 5 of 10 patients, a the remainingfour patients, no significant asymmetiy of significantly higher binding was found in the striatum con striatal receptor binding was detected. This finding of a tralateral to the direction of the torticollis (p = 0.026, higher dopamine D2 receptor density in the striatum con chi-square test, Figs. i and 4). In 4 of iO patients, no tralateral to the direction of head rotation was statistically significant interstriatal difference of IBZM binding was significantfor this patientgroup. These findingswere con noted. In one patient (P3), lower bindingwas found in the sistent with recent investigations publishedby Leenders et striatum contralateral to the direction of the torticollis. al. (12) andBrUckeet al. (11)who also found a tendency of MRI of the brain did not reveal any focal lesions within a higherD2 receptorbindingin the striatumcontralateralto the basal gangliaor the cerebellum in patients or controls. the direction of head rotation in a small group of patients One patient (P6) and one control (C5) showed periventric with CD. Such a unilateraldopaminereceptordeficitwould ularwhite matterlesions but not within the basal gangliaor be consistent with the animaldata of Crossman and Sam the cerebellum. One control patient (CS) had mild brain brock (8) that show that the relatively hyperactive normal atrophy. One control subject (Ci) had focal atrophywithin stnatum drives the head to the contralateral side. The the rightpanetal lobe thatwas consistent with an old brain primary striatal abnormality leading to a D2 binding asym infarct. metiy remains, however, unclear. It could reflect presyn aptic dopaminergicchanges leading to secondary D2 up DISCUSSION regulation or a primary postsynaptic deficit leading to The mechanismunderlyingIRTis not completely under reduced D2 receptor density. In one patient (P3), a higher stood to date. However, it is widely accepted thatthe basal receptorbindingwas found in the striatumipsilateralto the ganglia are involved in the pathophysiology of IRT (4â€”8). direction of head rotation. This finding could explain the Turning behavior and head rotation, in particular, have observation that, not infrequently, a bilateral affliction of been studied in various animal models. Hassler and muscle groups is observed in IRT, and the head rotation Dieckmann (25) suggested that the head rotates to a direc can be the resultof complexbilateralmuscleactivity(31). tion contralateralto the abnormalhemispherebecause the In the remainingfourpatients, no significantasymmetryof affected putamen does not inhibit tonic contraversive pal the receptor bindingwas found. This phenomenon might

IBZMSPECT in IRTâ€¢Hierhoizerat al. 1925 indicate differentstages of IRT. However, no correlation not observed with age or duration of the disease in this was found between the duration ofthe disease and receptor study. binding. The age-dependentvariation of D2 receptors has been PET studies that measured the presynaptic â€˜8F- studied with controversial results in healthy volunteers fluorodopa uptake in patients with dystonia indicated (35â€”37).The most severe decrease of D2 receptors with changes in dopa metabolism that lead to a reduced endog age has been shown to take place within the first30 to 40 yr enous dopamine pool rather than diminished nerve termi of age (35,36), although in elderly persons no furthersig nals arising from the nigrostriatalprojections (10). These nificant decrease has been described. This might be the presynapticchanges could be responsible for the postsyn reason why no correlationwith age was found in this rel aptic phenomena observed in the present study. A similar atively older populationof patients and controls. mechanism was proposed in patients with untreated Pa kinson's disease and with schizophrenia in whom a de CONCLUSION crease of nigrostriatal dopaminergic neurons and a de It was concluded from this study that the striatal dopam creased endogenous dopamine concentration might lead to inergic system and, particularly,the postsynaptic striatal an upregulationof striatal dopamine receptor sensitivity dopamine D2 receptors may be involved in idiopathic dys (32,33). However, these results remain controversial tonic diseases, such as IRT. This findingprovides further (18,34). Because of the small number of patients, the re support for the hypothesis of an involvement of the basal sults of the present study yield preliminaiy semiquantita gangliain the pathophysiology of idiopathic dystonia. tive data on striatal dopaminergicfunction in IRT. These findings must be interpreted with caution, and several ACKNOWLEDGMENTS problems concerning the selection of the patients, the study design and the method have to be discussed. This study is dedicated to Prof. Dr. A. Kaul, Director of the First, the clinical spectrum of diseases with dystomc BundesamtfÃ¼rStrahlenschutz,Berlin,ontheoccasionofhis60th movement disorders is wide, and different underlying birthday. mechanisms could be responsible for the symptoms of the Theenthusiasticintellectualsupportof Dr.PaulWolf,Profes sor of Pathology, U@SDMediCalCenter (San Diego, CA) is subjects described in this report. To select a clinically deeply appreciated. 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IBZMSPECT in IRTâ€¢Hierhoizerat al. 1927