Evaluation of the Effect Oftreatment on Movement Disorders In

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Journal ofNeurology, Neurosurgery, and Psychiatry 1993;56: 1113-1118 1113 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.10.1113 on 1 October 1993. Downloaded from Evaluation of the effect of treatment on movement disorders in astrocytomas of the basal ganglia and the thalamus

Joachim K Krauss, Dieter F Braus, Mohsen Mohadjer, Fritz Nobbe, Fritz Mundinger

Abstract Methods Twenty patients with movement disor- A total of 225 patients had astrocytomas ders associated with astrocytomas (grade grades I-IV of the basal ganglia or the thala- I-IV according to the WHO tumour clas- mus confirmed histologically by stereotactic sification) of the basal ganglia and the biopsy between 1965-86 in the department of thalamus were evaluated for the effects stereotaxy. Twenty were identified as having of treatment. Five patients had more an MD at the time of biopsy.5 The patients than one movement disorder when the were followed up and examined at various histological diagnosis was verified by times with recent follow ups in 1989, 90 or stereotactic biopsy. Twelve had tremors, 91. No follow up data concerning the tremor eight hemidystonia, three hemichorea, in patient 16 could be obtained. Some and one hemichorea/ballismus, and patients had serial film recordings over the myoclonus respectively. Ten patients years. Most of the long term surviving died during the follow up period, and for patients returned at regular intervals for con- the surviving patients foilow up periods trol CT scans. In addition, the relatives, ranged from 6-21 years. The movement attending physicians and neurologists were disorders changed over long periods of interviewed to compile the data. time related to therapeutic interventions. Stereotactic biopsy was performed under CSF shunt operations and percutaneous local anaesthesia, except in the younger radiotherapy had no definite effect on the children. Tumour site, volume and the irradi- movement disorders. There was a mod- ation dosimetry were determined from CT erate response to medical treatment in a data available since 1975. The Riechert- few patients. Stereotactic aspiration of Mundinger stereotactic device in the com- tumour cysts had a marked influence on puter-compatible version was used for the movement disorder in two patients, stereotactic biopsy, interstitial implantation of and functional stereotactic surgery abol- radioactive isotopes, cyst aspiration and func- ished tumour induced tremor in one. tional stereotactic surgery. The principles and Interstitial radiotherapy was performed methods are described in detail elsewhere.21-26 in fifteen patients for treatment of the The decision whether or not to perform inter- underlying neoplasm and resulted in dif- stitial radiotherapy was made according to the

ferent and variable alterations of the clinical state of the patient, the tumour size http://jnnp.bmj.com/ movement disorders. These differences and the results of the intraoperative smear may be explained by complex interac- preparation. The presence of an MD was not tions involving structures affected pri- relevant. Interstitial radiotherapy was per- marily by the tumour, as weli as by formed in the same session via the puncture Department of secondary functional lesions of adjacent track for biopsy. To produce radionecroses of Neurosurgery, Albert- structures. the tumours the radioactive isotopes 125I Ludwigs-Universitat, Freiburg (half-life 60-2 days, photon energy spectrum J K Krauss ( Neurol Neurosurg Psychiatry 1993;56: 1113-1118) ranging between 27 and 35 keV) and 192Ir on September 29, 2021 by guest. Protected copyright. F Nobbe (half-life 74-2 days, energy spectrum ranging Department of from 300 to 610 keV) were used. The periph- Stereotaxy and Neuronuclear eral tumour accumulation dose (that is, at the Medicine surface of the tumour) ranged from 90 to 120 M Mohadjer Movement disorders (MDs) in tumours of Gy. It was exceptionally high in patient 10 Zentralinstitut fulr the basal ganglia and the thalamus have been (150 Gy), and low (50 Gy) in patient 3. It Seelische Gesundheit described within a range from 1-9% in recent was generally lower in more recent years. Mannheim D F Braus studies and from 4-33% in earlier ones.1-5 Shunts placed were either ventriculoatrial St. Josefs- The further course following treatment has or ventriculoperitoneal, and if necessary, Krankenhaus, been documented only rarely in patients with bilateral. Freiburg, Germany MDs due to basal ganglia and thalamic F Mundinger astrocytomas.620 This study deals with the Correspondence to: Dr Krauss, clinical course and the change and outcome Results Neurochirurgische of MDs in relation to treatment of either the The study consisted of eleven female and Universitatsklinik, Hugstetter Str 55, D-7800 tumour responsible for them or of the symp- nine male patients. The age at biopsy ranged Freiburg, Germany. tomatic MDs themselves in twenty patients from three to 70 years (table). Demographic, Received 2 September 1992 with basal ganglia and thalamic astrocytomas clinical and neuroradiological data have been and in final revised form 11 December 1992. grade I-IV presenting with MDs at the time reported recently.5 Ten patients were alive on Accepted 18 December 1992 of biopsy. recent follow up. Follow up periods ranged 1114 Krauss, Braus, Mohadjer, Nobbe, Mundinger J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.10.1113 on 1 October 1993. Downloaded from Demographic data, treatment andfollow-up of20 patients with movement disorders in basal ganglia and thalamic astrocytomas. Sexl Grade Age at Biopsy Movement ofastro- Follow KPS: Interstitial Shunt Movement disorder Case Age at Onset disorder cytoma Status up alb curietherapy operation Other treatment Course-Outcome 1 M/25/13 Tremor, 3-4 Hz I A 12y 60/80 - + (-12y) Perc. radiotherapy (- 12y) Dis of tremor after 1 arm: Stereotactic aspiration of cyst aspiration rest, post, int r thalamic tumour cyst (0) 2 M/3/3 Tremor, 3-5 Hz D 6m 80 I-125 + (4m) Perc, radiotherapy (- 4m) Inc of athetosis (4w), 1 arm > leg: post, int temporary imp with Athetosis, 1 hand: rest corticosteroids (2m) Head tilt 3 M/50/44 Tremor, 3-4 Hz A 8y 60/70 I-125 - Medication with biperiden Tremor unc after curie- 1 arm > leg: therapy, slight imp after rest, post, int biperiden 4 Ff49/43 Chorea II D 2-5y 60 a: Ir-192 - Perc, radiotherapy (-4y) a: Inc ofhemichorea (6m) face bilat, 1 > r II-III b: Ir-192 Medication with haloperidol b: 2 w after 2nd stereotactic 1 arm > leg (8m) (8m) (8m) operation imp of chorea with haloperidol, dis 2 w later 5 F/70/70 Parkinsonism IV D Im 40 + (-1w) - Parkinsonian symptoms unc 6 M/37/31 Tremor, 4-5 Hz II D 4y 60 - - - Fluctuation of intensity of I arm: tremor, presumably related rest, post, int to medication with corticosteroids 7 F/11/10 Dystonia I A 9y 60/70 I-125 + (-3m) Stereotactic aspiration Inc ofhp and dystonia (0,5-ly) 1 arm: of tumour cyst (2y) imp of hp + dystonia (3y), rest, on action 2nd stereotactic aspiration inc of hp + dystonia (6-7y) of tumour cyst (8y) imp of hp + dystonia (8y) 8 M/12/9 Dystonia I A 13y 70/80 a: Ir-192 + (1w) - a: imp of tremor + hp (6m), 1 hand: on action b: Ir-192 + (2y) b: unc in further course Tremor, 4-5 Hz (9m) 1 arm: post, int 9 M/42/41 Tremor, 4 Hz II D 2-5y 70 - - Medication with biperiden, No response of tremor to r arm: later with metixen biperiden, imp after metixen rest, post, int (ly), later red of tremor with parallel app ofhp 10 M/25/25 Dystonia I A 20y 60/60 a: Ir-192 a: inc of hp and dystonia r arm: b: Ir-192 over years, no change in b: rest, on action (18y) further course 11 M/15/13 Tremor, 4-5 Hz I A I Oy 70/60 I-125 - Various medication Inc of tremor after r arm: thioridazine, no response to rest, post, int trihexyphenidyl, imp after biperiden, inc ofhp, dis of tremor (6 m), spastic hp (7y) 12 F/11/9 Chorea II A 21y 70/80 Ir-192 + (-2y) - Dis of chorea without inc r arm > leg of hp (05y), no MD in marked on action further course 13 F/10/9 Dystonia I D 5y 60 a: Ir-192 + (4y) a: Dis of chorea + ballismus, 1 arm > leg III(4y) b: Ir-192(ly) inc of dystonia + hp (05y) Chorea-Ballismus 1 arm > leg 14 F/12/3 Tremor, 3-5 Hz II A 6y 60/70 I-125 + (-3m) - post shunt imp ofhp, no effect I arm: on tremor (- 2m), inc oftremor rest, post, int (8m), imp of tremor + app of mild dystonia arm (2y) 15 M/16/15 Dystonia + Chorea D 3d 40 - + (2d) - Postop inc of obtundation, 1 arm> leg> face: coma (possibly related to rest, on action inc of edema), death 16 Ff62/59 Tremor, high- D 6m 60 I-125 unknown unknown frequency bilateral, 1 > r fingers + eyelids 17 F/13/11 Dystonia, r arm: I D 5y 70 a: Ir-192 + (4d) Imp of dystonia, dis of rest, on action b: Gamma myoclonus (2y) Myoclonus, r shoulder Med (4y) http://jnnp.bmj.com/ 18 Ff3/2 Tremor, 3-4 Hz I D 11i5y 70 a: Ir-192 + (2w) a: Dis of tremor (6m) r arm: int b: Ir-192 (3y) c: Ir-192 (lOy) 19 F/5/5 Dystonia, r arm: I A 16y 60/70 a: Ir-192 + (ly) a: imp of dystonia + hp (3m), rest, on action b: Ir-192 inc of dystonia + app of r (ly) chorea (ly), b: inc ofhp, imp of dystonia, disofchorea (3y) 20 F/12/10 Tremor, 3-4 Hz I A 20y 60/70 a: Ir-192 - Functional stereo- a: Imp of hp + tremor (ly), on September 29, 2021 by guest. Protected copyright. r arm: int b: Ir-192 tactic operation (4y), inc of hp + tremor (3y), (4y) Stereotactic aspiration b: dis of tremor after of tumour cyst (1 5y) functional stereotactic operation, no recurrence of tremor Sex: M = male, F = female. R = right, L = left. Tremor: is qualified as: rest - tremor at rest, post - postural tremor and int - intention tremor. Status: A = alive (at last follow up available), D = dead. Follow up: is defined as time of survival after stereotactic biopsy at last follow up or until death. KPS (Karnofsky Performance Scale): a: preoperative/b: at last follow-up. All intervals of time refer to stereotactic biopsy: d = days, w = weeks, m = months, y = year(s), - = prior to biopsy. Movement Disorder Course - Outcome: hp = hemiparesis, app = appearance, inc = increase, unc = unchanged, imp = improvement, red = reduction, dis = disappearance.

from 6-21 years (mean 13-5 years). There 21 years after biopsy. In two patients anaplas- were no post operative complications except tic transformation was found on rebiopsy. in patient 15. This 16 year old boy with a Only patients with low-grade astrocytomas thalamic glioblastoma extending to the upper survived more than five years. With the brainstem was in a poor condition when exception of case 11, all patients who were referred. He deteriorated further after biopsy alive on recent follow up were stable or had and died three days later, probably due to an improved Karnofsky Performance Scores.27 increase in intracranial pressure. In the other MDs in this selected group of patients patients survival ranged from one month to changed over long periods of time. In most Evaluation ofthe effect oftreatment on movement disorders in astrocytomas of the basal ganglia and the thalamus 1115 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.10.1113 on 1 October 1993. Downloaded from therapy, however, over this period hemidys- tonic postures appeared. Transient hemichorea was observed one year after interstitial radiotherapy in patient 19.

OUTCOME IN RELATION TO TREATMENT MODALITY .4 In no patient was partial or radical tumour resection attempted. Interstitial radiotherapy This was done in 15 patients. 6 were implanted twice, one patient on three occasions. During the first 3-12 months after interstitial radiotherapy, the MD increased, at least temporarily, in some patients (cases 2, 4, 7, 10, 14). CT Figure I Axial enhanced CT scans ofpatient 7 with dystonia ofthe left arm due to a scans showed signs of radionecrosis with grade I astrocytoma located predominantly in the rightpallidum and subthalamic region. varying degrees of perifocal white matter The patient has a second tumour extendingfrom the quadrigeminalplate to the pons and cerebellum. a) Before interstitial radiocurietherapy. b) 8 months after implantation of a oedema (fig 1), depending on the dose and l25I seed a cyst developed. c) 18 months after interstitial radiotherapy the cyst enlarged. At the isotope applied. Twelve to 24 months that time, dystonia and hemiparesis had increasedfurther. d) 24 months after interstitial after the operation, the MD had subsequently radiotherapy the cyst was aspirated stereotactically and a drainage was placed. The dystonia and the hemiparesis improved significantly. improved in patients 7 and 14 to be less severe than preoperatively. However, in other patients who also had signs of radionecrosis cases these changes were temporally related on CT controls, the MD improved (cases 8, to therapeutic interventions (as described 17, 19, 20) or even disappeared during the below), or to recurrence or regrowth of first months following interstitial radiotherapy tumour as diagnosed neuroradiologically. (cases 11, 12, 17, 18). In three patients a Increase of hemiparesis was associated with later increase of the MD indicated tumour reduction of the MD in patients 9, 11 and 19. recurrence or cyst formation (cases 7, 19, However, in other patients a parallel improve- 20). In patient 10 with a grade I astrocytoma ment of the hemiparesis and the MD could located mainly in the left lenticulostriate area, be observed (cases 7, 8), or conversely a par- hemidystonia increased over many years after allel increase of the hemiparesis and worsen- interstitial radiotherapy. CT controls did not ing of the MD (cases 10, 13). show local tumour recurrence; however, a porencephalic defect had developed in the OUTCOME IN RELATION TO TYPE OF region where the tumour was previously MOVEMENT DISORDER located. No signs of tumour recurrence on The overall outcome of the MD at the last the last follow up were found in patients 3, follow up, without respect to therapeutic 11, 12, 14, 19 and 20 (fig 2). The MD was strategies, was as follows: hemichorea and no longer present in three of them (cases 11, hemichorea/ballismus disappeared in three 12, 20) and had improved in three others patients (cases 4, 12, 13); myoclonus disap- (cases 3, 14, 19/ case 14 developing hemidys-

peared in one (case 17); tremor disappeared tonia). http://jnnp.bmj.com/ in three patients (cases 1, 18, 20), improved Functional stereotactic surgery The right to some degree in five (cases 3, 8, 9, 11, 14), intention tremor and hemiparesis of patient fluctuated in one (case 6), and did not change 20 (grade I astrocytoma of the left thalamus in two (cases 2, 5); hemidystonia improved to extending to subthalamus and crus cerebri) some degree in three patients (cases 7, 17, which had improved one year after interstitial 19), fluctuated in one (case 2), did not radiotherapy with '92Ir worsened again con- change in one (case 8), and worsened in two siderably on tumour regrowth after three (cases 10, 13). In patient 14 with a grade II years. One year later a stereotactic biopsy on September 29, 2021 by guest. Protected copyright. astrocytoma of the right thalamus extending from the centre of the tumour, which was to the midbrain, contralateral tremor located more posteriorly in the thalamus, ver- improved two years after interstitial radio- ified tumour recurrence, and another course of interstitial radiotherapy with 192Ir was given. A biopsy was then taken from the left zona incerta, which did not show tumour cells. Following electrical stimulation, two electrocoagulations were done at the site of the biopsy in the zona incerta. The tremor had disappeared completely postoperatively and did not recur. Stereotactic aspiration of tumour cysts Two patients had tumour cysts aspirated. Patient 1 had a left 3-4 Hz resting, postural and intention tremor, which disappeared completely after aspiration of a right thalamic tumour Figure 2 Axial enhanced CT scans ofpatient 19, 14 years after interstitial radiotherapy cyst extending to the midbrain and did not with '92Ir. The patient hadpresented with dystonia of the right arm due to a grade I recur during the 12 year period of follow up astrocytoma of the left thalamus and basal ganglia. She also had transient right hemichorea. The CT scans demonstrate the late effects of radionecrosis with metallic (fig 3). Patient 7 showed improvement of left artefacts ofthe '92Ir wires, calcifications and gliosis. There is no evidence ofresidual tumour. hemiparesis and hemidystonia after aspiration 116 Krauss, Braus, Mohadjer, Nobbe, Mundinger J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.10.1113 on 1 October 1993. Downloaded from tion,68913 "paleating operation","1 subtotal'0 and total extirpation.'2 Regardless of which technique was applied, the results in general were poor and the majority of patients died within two months after operation, many of them in the first postoperative days. There are no previous reports on long term follow up, and few data on the subsequent evolution of the MDs. Disappearance or relief of the MD postoperatively was reported after partial resection of tumours affecting parts of the hemisphere and the basal ganglia in three patients: remission of Parkinsonian symptoms,"3 marked decrease of intention tremor6 and disappearance of tremor and rigidity.9

Figure 3 Axial enhanced CT scans ofpatient 1 who presented with left resting, postural One recent patient with a frontotemporal and intention 3-4 Hz tremor show a cystic pilocytic grade I astrocytoma located in the astrocytoma grade I had temporary improve- right thalamus. The tremor disappeared after stereotactic aspiration of the tumour cyst. ment of hemidystonia after a frontal lobec- tomy.'5 "Disappearance" of dystonia or choreoathetosis was also reported after of a tumour cyst located mainly in the right removal of basal ganglia or thalamic astrocy- pallidum and subthalamus two years after tomas, but those patients were hemiplegic interstitial radiotherapy (fig 1). The same postoperatively." 12 In two patients with effect was achieved six years later. tremor, stereotactic resection of a low-grade Percutaneous radiotherapy Three patients astrocytoma of the thalamus was performed' had undergone external beam radiation 16 resulting in mild improvement of tremor six before biopsy. Patients 1 and 4 had no MD at months later in one of them.'6 that time and in patient 2 no obvious alter- Functional stereotactic surgery was only ations were noted. rarely carried out in patients with MDs due CSF shunts In 12 patients enlarged ven- to tumours or secondary to treatment of tricles were shunted at some time during their tumour.2830 To our knowledge, its use has disease. Three patients had had no MD when never been described in a patient with symp- the shunt was placed and in six patients no tomatic MD due to a thalamic astrocytoma. effect on MDs was observed. A positive effect Shunt operations have been reported to alter of shunting may not be excluded totally in MDs in patients with hydrocephalus.31 32 two patients with hemidystonia and one with However, there was no unequivocal effect on tremor, though improvement was more prob- the MDs after shunt operations in the present ably related to interstitial radiotherapy. series. For most previously reported cases, Multiple revisions of shunts had no influence the effect of percutaneous radiotherapy on on MDs in seven patients (cases 1, 5, 7, 8, the MD was either not recorded or was 12, 17, 19). doubtful.81012171820 In two patients with Pharmacological trials It was difficult to hemidystonia due to contralateral tumours of assess the response to drugs. Many patients the basal the was ganglia MD reported to http://jnnp.bmj.com/ took corticosteroids for some time during the have improved to some degree after percuta- course of their disease. In patient 6 with a neous irradiation.'519 large diffuse low-grade astrocytoma of the Experience with medication for MDs sec- right thalamus, basal ganglia and hemisphere ondary to astrocytomas of the basal ganglia fluctuation in intensity of tremor was related and the thalamus is very limited. Apart from to the dose of corticosteroids. Patient 2 with a one report stating that anti-Parkinsonian drug mainly thalamic grade I astrocytoma showed therapy had no benefit on Parkinsonian a slight improvement in athetosis after corti- symptoms in a 62 year old male with a grade on September 29, 2021 by guest. Protected copyright. costeroid therapy. Tremor improved slightly II astrocytoma of the thalamus,'4 we found no in patients 3 and 11 after treatment with other remarks on the effects of drug therapy biperiden, whereas no effect on tremor was on tremor. No data are available from the lit- noted in patient 9, who improved after taking erature on medical treatment of chorea or metixen. Tremor increased after thioridazine "choreoathetosis". Moderate improvement of in patient 11. Chorea in patient 4 with a right hemidystonia after carbamazepine was frontocaudate astrocytoma improved two described in an eight year old boy with a con- weeks after the second course of interstitial tralateral low-grade astrocytoma located radiotherapy while she took haloperidol and mainly in the putamen and pallidum.'9 disappeared completely two weeks later. We could not find previous reports on the effect of interstitial radiotherapy on MDs in astrocytomas of the basal ganglia and the Discussion thalamus, which as demonstrated, may have The majority of patients with MDs secondary complex effects on the later evolution of the to basal ganglia and thalamic tumours col- MDs. lected from the literature were reported more Interpretation of the data on alterations of than three decades ago, most of them having MDs in patients with tumours of the basal had open surgery. Operations performed were ganglia and the thalamus-particularly the described as subtemporal decompression,67 alterations after interstitial radiotherapy- exploration,6 open biopsy,10 " partial resec- needs to consider different variables that may Evaluation ofthe effect oftreatment on movement disorders in astrocytomas ofthe basal ganglia and the thalamus 1117 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.10.1113 on 1 October 1993. Downloaded from or opposing actions in We thank G Pfister, H F6rster, K Roskamm and V Sonntag- have either synergistic O'Brien for technical assistance and preparation of the an individual patient, and thus produce com- manuscript. pletely different results. We have proposed that MDs in those patients might result from structural lesions as well as from functional damage of structures involved primarily by 1 Kelly PJ. Stereotactic biopsy and resection of thalamic astrocytomas. Neurosurgery 1989;25:185-95. the tumour ("internal" compression) or of 2 Bernstein M, Hoffman HJ, Halliday WC, Hendrick EB, adjacent regions ("external" compression).5 Humphreys RB. Thalamic tumors in children. J7 Neurosurg 1984;61:649-56. These interactions may account particularly 3 McKissock W, Paine KWE. Primary tumours of the for the change of MDs in patients who had thalamus. Brain 1958;81:41-63. 4 Tovi D, Schisano G, Liljequist B. Primary tumors of the treatment resulting in modifications of local region of the thalamus. J Neurosurg 1961;18:730-40. pressure. Thus, for example, disappearance 5 Krauss JK, Nobbe F, Wakhloo AK, Mohadjer M, Vach W, Mundinger F. Movement disorders in astrocytomas of tremor in patient 1 after decompression by of the basal ganglia and the thalamus. Jf Neurol aspiration of the thalamic tumour cyst proba- Neurosurg Psychiatry 1992;55:1162-7. 6 Ody F. Tumors of the basal ganglia. 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