Tiirkis/i Neiirosiirgery 11: 1 - 8, 2001

A Review OfTreatment Of

Emphasis

Berk: SlIrgery for Parkiiisoii 's disease

Current Surgical Options For TheParkinson's Disease, With SpecialOn Deep Brain Stimulation

Parkinson hastaliginin cerrahi tedavi secenekleri vederin beyin stimulasyonu

ÇACLAR BERK

Surgical Centre for Movement Disorders, University of British Columbia, Vancouver, BC, Canada.

Received : 20.3.2001 ~ Accepted : 25.4.2001

Abstract: Surgical treatment of movement disorders, andespecially Parkinson's disease, is regaining momentum.Despite all efforts, a significant number of patients whosuffer from various types of movement disorders arebecoming surgical candidates. Recent advances inmedical technology have enabled more precise targetingof deep brain structures, as well as reversible modulationof the neural outputs. Utilization of these technologies incommon practice may well expand our options fortreating complex movement disorders. Deep brainstimulation is one of these promising advances instereotactic surgery for movement disorders. This reviewbegins with a historical perspective, and then presentsthe latest knowledge in this field. The intent was to informhealth care providers in neurological sciences about theimplications, application, and scope of this technology.

Key words: Deep brain stimulation, movement disorders,Parkinson's disease, stereotaxis, surgery

INTRODUCTION

Mavement disorders are a group of neurologicalconditions that share the comman feature of

disrupted control of body mavements. The best­recognized condition is Parkinson' s disease (PO), but

Özet: Medikal tedavideki tüm yeniliklere ragmen hareketbozukluklarinin cerrahi tedavisine gerek duyulan hastave yapilan ameliyat sayilari giderek artmaktadir.Parkinsor, hastaligi cerrahi olarak tedavi edilen hareketbozukluklari içerisinde önemli bir yer tutmaktadir. Tipteknolojisindeki ilerleme artik derin beyin yapilarinin cokdaha duyarlilikla belirlenip hedeflenebilmesine veburadaki aktivitenin degistirilebilmesine olanaktanimaktadir. Derin beyin stimulasyonu bunlarin enonemlilerindendir. Bu teknolojilerin yaygin kullanimagirmesiyle birlikte stereotaktik hareket bozuklugucerrahisinin ufku daha da genislemistir. Bu derlernedehareket bozuklugu cerrahisinin tarihsel gelisimi,günümüzde yaygin kullanilan cerrahi hedefler, derinbeyin stimulasyonu teknolojisi ve uygulamalarininsonuçlari gözden geçirilerek bu konularda çalisanlaragenel bir görüs kazandirilmasi amaçlanmistir.

Anahtar Kelimeler: Cerrahi, derin beyin stimulasyonu,hareket bozuklugu, Parkinson hastaligi, stereotaksi

others include chorea, dystonia, and tremor dueto a variety of causes. These conditions consumea large portian of health care resourees, andproduce incalculable patient suffering. PO alonecosts the United States an estimated $25 billian each

year.

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Turkis/i Neiirosiirgery 11: 1 - 8, 2001

Parkinson's disease is a progressivedegenerative disease of the basal ganglia.Pathologically, it is characterized by the loss ofdopaminergic cells of the substantia nigra (SNr) andpars compacta (23). The major dopaminergicprojection from the SNr (nigrostriatal tract)innervates the striatum, although dopaminergic SNrneurons als o innervate other regions of the basalganglia involved in motor control (7,23,31). Thecardinal signs of PD are resting tremor, rigidity,bradykinesia, and postural instability. The criteria forthe diagnosis of idiopathic PD include at least two ofthese four cardinal signs, as well as a history of abeneficial response to levodopa (L-dopa).

Historical Background

Surgeryon basal ganglia structures waspioneered by Meyers in 1939 (33). As more casesaccumulated, Meyers surgically experimented withextirpation or sectioning of various portions of thecorpus striatum and related pathways, and showedthat tremor could be abolished and rigidity reducedwithout the production of paresis, spasticity, ordyspraxia (32). Meyers' work was followed by thatof Browder and Hamby, whose promising resultswere accompanied by high mortality (8,21). Thesehigh mortality rates with the transventricularapproach led Fenelon to develop a free-han dtechnique for passing an electrode via an anteriorsubfronta!, a transtemporal, or a transfrontalapproach to directly coagulate the ansa lenticularis(15). Guiot and Brion reported asimilar techniquefor direct coagulation of the globus pallidus and ansalenticularis in 1953 (19). Later, Bertrand was able tosurgically isoIate the pallidal area (6). Cooperinvestigated the effects of basal ganglia lesions inmovement disorders after an incidental anterior

choroidal ar tery injury, but finally abandoned thistechnique due to unpredictable results related toanatomical variations in the anterior choroidal arteryand its territory (11).

The unacceptable morbidity associated withopen surgery for neuroablative proceduresmotivated researchers to develop safer methods. In1948, Spiegel and Wycis pedormed the firststereotactic pallidotomy and thalamotomy on record(43). Soon after that, stereotactic techniques withmany variations began to be performed around theworld. In 1951,Narabayashi and Okuma tried to treatPD by injecting an oil-wax mixture into the globus

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Berk: Siirgery for Pnrkiiisoii's disease

pallidus (35). In the same year in Germany, Hasslerand Riechert became the first to produce a stereotacticlesion in the ventrolateral nucleus of the thalamus as

treatment for PD (22). Mundinger explored thesubthalamic nuclei (STN) for the treatment of PD,intentional tremor, and myoclonic-ballistichyperkinesia (34).

By 1965, it was estimated that more than 25,000procedures for parkinsonism had been performedworldwide (42). However, with the development ofL-dopa treatment, functional neurosurgicalprocedures declined dramatically after 1968 (12). Fordecades, the surgical treatment of PD was practicallywithdrawn from the therapeutic arsenaL. In the early1970s, the follow-up examinations of L-dopa treatedpatients began to reveal some drawbacks of thesubstitutive treatment; such as intolerance, loss ofefficacy, or even added complications such asabnormal involuntary movements. This marked thebeginnings of a renewed need for surgical treatmentand better understanding of the anatomy andphysiology of the basal ganglia. This need, coupledwith improved imaging modalities, the ability toneurophysiologically identify the deep brainstructures, and continued progress in surgicaltechnology, led to the resurrection of stereotacticsurgery for movement disorders.

Today, the thalamus, globus pallidus, and STNare widely used as effective targets for variousmovement disorders and for parkinsonism. Theadvent of deep brain stimulation (DBS) technologyenabled us to perform bilateral, reversible, and,perhaps most important, specially tailoredinterventions for all the above-mentioned targets.These procedures favor a restoratiye approach to thecentral nervous system as a means of resolvingcomplex neurological problems.

Mechanism of Action and SurgicalTechnique for Deep Brain Stimulation

Most patients with movement disorders aretreated effectively with medications. A smaIl portion,however, have refractory symptoms. Some of thesesymptoms can be treated with neurosurgicalinterventions. Over the years, the safety and efficacyof these procedures have improved with theintroduction of stereotaxis, radiofrequency lesioning,non-invasive imaging, and now DBS. Before theintroduction of DBS, neurosurgeons could only

Tiirkish Neiirosiirgery 11: 1 - 8, 2001

destroy the overactive brain regions responsible formovement disorders. The effects of these lesions

(usually beneficial but occasionally detrimental)are permanent. Deep brain stimulation is designedto "turn off" these overactive brain regionswithout destroying them. The immediate advantageof DBS over conventional destructive neurosurgeryis that the "lesions" are titratable and, hence,reversible.

it is currently accepted that many of thesymptoms of PD are due to overactivity of theinhibitory pallidofugal pathways originating fromthe internal pallidum (GPi), the GPi being driven inpart by overactive STN. The net effect is the inhibitionof cortically mediated impulses via thethalamocortical loop (30). Because of the currentknowledge of their anatomical relationships andphysiological functions, and the ease with whichthese structures can be access ed through currentneurosurgical techniques, the thalamus, Gpi, andSTN are suitable targets for both stereotactic lesioningand neuromodulation using DBS.

Theoretically, DBS can influence both neuronsin the target structure and fibers passing or borderingthat structure (44). it is still not known how the

functional suppression of these targets occurs at theceIlular leveI. The effects are frequency-dependent.An effect can be detected with frequencies above 50Hz, and reaches maximum at 100-200 Hz. High­frequency stimulation has been used as anintraoperative test for optimal targeting for severalyears (44,48). The implantation of a chronic DBSelectrode was initially proposed as an experimentaltherapeutic procedure (44). When the results wereexcellent, a pilot study was launched for patients whohad undergone previous thalamotomy and requireda second operation on the contralateral side (5).Whenthese results were also encouraging, DBSapplicationswere extended to treat other types of movementdisorders (3,4,5,16,17,29).

The Hardware

There are three components to the DBS system(ActivaTM, Medtronic Inc., Minneapolis, MN, USA).The first is the DBS lead. The tip of this insulatedlead has four platinum/iridium electrodes spaced 0.5or 1.5 mm apart. These electrodes are placed withinthe target brain region and are used to deliver thehigh-frequency stimulation designed to block or

Berk: Siirgery for Parkiiisoii's disease

disrupt the function of the surrounding brain. Aninsulated cable, the extension, is tunneledsubcutaneously from the DBS lead to its powersource. The implantable pulse generator (IPG)(ItrelTM II/III, SoletraTM, Medtronic Inc.,Minneapolis, MN, USA) is placed in a subcutaneouspocket below the clavicle and provides both thepower for stimulation and the ability to use telemetryto control the stimulation parameters. The final sizeof the "lesion" is adjusted in the outpatient clinic aftersurgery by changing these stimulation parameters.The DBS effects can then be tailored to the

individual's symptoms, enlarging the "lesion" toincrease beneficial effects or reducing its size to avoida side effect. Figure 1; illustrates the DBS systemhardware and the implanted electrode within thethalamus.

The Surgery

There are two parts to any DBS operation:implantation of the DBS lead within the brainand insertion of the IPG. The details of targetingare beyond the scope of this review, butany neurosurgical center with stereotacticexperience and appropriate training can perform theoperation.

Figure 1: An artist's drawing iiiustrates the DBS systemand the electrode implanted in the thalamus.

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Turkis/i Neurosiirgery 11: 1 - 8, 2001

Implantation Of the DBS Lead:

At the Surgical Centre for Movement Disorders,University of British Columbia, we use a magneticresonance imaging-compatible head frame (UCLF,Radionics Ine., Burlington, MA, USA) for patientswithout tremor, and a computed tomography (CT)­compatible frame (CRW, Radionics Inc., Burlington,MA, USA) for those with tremor. Frames are placedusing local anesthetic and no sedation is given duringthe procedure. Patients receiye preoperativeantibiotics on transfer to the operating room. The hairis shaved over the coronal suture and the scalp isprepared, draped, and infiltrated with localanesthetic. A 14-mm burr hole is drilled in the skull

and the dura is opened. The are system is thenattached to the head ring. The brain target area canbe localized with either macrostimulation or

microelectrode recording. Once the probe has foundthe target area, it is replaced by the DBS lead underfluoroscopic guidance. The lead is locked in placewith a burr hole button and the scalp is temporarilyclosed.

Insertion of the IPG:

Early in our experience, this portion of theprocedure was often performed several days later.Patients with a temporary external extension fromthe DBS lead to a hand-held trial stimulator were

monitored for their response to a variety ofstimulation settings. if a good response wasconfirmed, we would then proceed to implantationof the IPG. More recently, we have been combiningthe two procedures after intraoperative confirmationof target localization. During insertion of the IPG,patients receiye a general anesthetic. Mostindividuals leave hospital the following day (after24 hours of antibiotics), although our multipleselerosis patients occasionally ne ed more time.The procedure involves making a subcutaneouspocket for the IPG below the clavicle and tunnelingthe extension cable from the scalp to the chest.

Various Targets Use d for Deep BrainStimulation

Thalamie DBS

Thalamotomy for the treatment of tremor wasintroduced nearly half a century ago (11,22). Theintroduction of L-dopa treatment and the morbidity

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Berk: Siirgen} for ParkinsolJ 's disease

related to thalamotomy (particularly with bilateralprocedures) made it an unfavorable therapy for PO(24). Even from the earliest days of stereotacticsurgery for PO, it was known that acute electricalstimulation at certain brain sites arrested the tremor

during stimulation; however, the exact mechanismsof this suppression with DBS are still not wellunderstood (4,44). Deep brain stimulation was notavailable as a treatment modality until1980s. In 1987,Benabid and co-workers succeeded in treatingparkinsonian patients with drug-resistant tremorusing chronic stimulation of the ventrointermediatenucleus of the thalamus (Vim) (6). After achievingsuccessful preliminary results, this group startedperforming Vim stimulation as a first surgical option,abandoning thalamotomy (4). In time, unilateral DBSbecame a widely accepted and applicable techniquefor the treatment of essential and parkinsoniantremor (24,36). Figure 2; shows the thalamictarget with respect to the posterior commissure onan axial CT section at the level of theintercommissuralline.

Retrospective analysis comparing thalamotomywith thalamic DBShas proven that DBSis as effectiveas thalamotomy for tremor control, and has fewerpotential complications and side effects (28,46,47). itis now widely accepted that bilateral implantationof the DBS electrodes does not carry the potentia!

figure 2: Fig 2: An axial CT sean at the level ai anteriorand posterior eommissures demonstrates thethalamic target point with respeet to posterioreommissure.

Tiirkis/i Neiirosiirgery 11: 1 - 8, 2001

risks of bilateral thalamic lesioning, such as cognitive,memory, language, swallowing, and speechdisturbances (4). Dysarthria more often affectspatients who have undergone previous contralateralthalamotomy than those who have been treated withbilateral thalamic DBS (4,5). A decrease in L-dopa­induced dyskinesia was reported in some patients(lO), but this effed was not found to be significant inother studies (28,48). The improvement of L-dopa­induced dyskinesias after thalamic DBS may beassociated with deeper and more rnedial placementof eledrodes (9). A recently published multicenterstudy shows that thalamic DBS may reduce tremorup to 85% in 12 months of follow-up (28). Both upperand lower limb tremor were reduced, and there wasa slight improvement of limb akinesia and rigidity.Speech, postural stability, and gait were notsignificantly improved, but the activities of dailyliving (ADL) scores improved as a consequence ofreduction in tremor. These results are comparablewith those of Vim thalamotomy (24). No publishedprospective randomized study has yet comparedthalamic stimulation and thalamotomy, but one iscurrently in progress in the Netherlands (41). Thereare also some recent promising reports about bilateralthalamic DBS for the treatment of isolated head andvoice tremors (45).

Pa Ilidal DBS

Pallidotomy was re-popularized after Laitinen'scornerstone work (27). The very encouraging effectsof ventroposterolateral pallidotomy on all symptomsof PD led to the introduction of an alternatiye

technique, that of permanent electrostimulation ofthe pallidum (40). The most dramatic effect ofpermanent bilateral ventroposterolateral stimulationin PD patients was the disappearance of severeiatrogenic L-dopa-induced dyskinesias (39). Inaddition, there was c1ear improvement in akinesiaor hypokinesia, as well as rigidity (l4,17,38,50).Patients who have undergone unilateral pallidotomymay experience increasing disability due to persistentand progressive signs on the non-operated side.Many neurosurgeons are reluctant to producebilateral destructive lesions based on the considerable

morbidity associated with bilateral thalamotomies.The reversible nature of DBSis preferred to a seconddestructive procedure. In patients who haveundergone prior pallidotomy, contralateralimplantation of a DBS electrode is a reasonablealternative to bilaterallesioning (l6).

Berk: Siirgery for Parkiiisoli'S disease

Although there are some controversial reportson the efficacy of bilateral pallidal DBS (49), thisvariable success may be related to the differentialresponse to stimulation in different parts of thepallidum (2). Stimulation of the lower(posteroventral) pallidum is reported to reduce L­dopa-induced dyskinesia dramatically, but canworsen parkinsonian symptoms (except rigidity) andeven block the beneficial effects of L-dopa.Stimulation of the upper (dorsal) pallidum improvesparkinsonism, but can induce dyskinesias in the "off"state and worsen them in the "on" state (2). Bilateral

pallidal stimulation may be considered aneffectjve and safe alternative for patients whohave L-dopa-responsive parkinsonism withuntreatable motor fluctuations. In such cases, thereis a mean improvement in motor and ADL scores ofover 50%, and the patients have no majorneuropsychological dysfunction that interferes withdaily activities (l7).

SubthalamIe Nuc1eI DBS

STN overactivity is a central abnormality in thebasal ganglia-thalamocortical circuit in theparkinsonian state. Because the projection from theSTN to the GPi is excitatory, one effect of interruptionof STN activity should be to correct overactivity inthe Gpi, producing an effect similar to pallidotomy.Theoretically, however, the STN may be an evenmore attractive target than the GPi for alleviation ofparkinsonian signs because it affects the function ofboth basal ganglia output nuclei (SNr and GPi). Thus,interruption of STN activity might potentiallyalleviate more motor abnormalities than interruptionof GPi activity alone. Based on these theoreticalconsiderations, current interest in the STN as asurgical target for PD is increasing (3,18,20,29). STNlesions have been performed in smail series ofpatients with results of considerable improvementin parkinsonism (l8), but lesioning of the STN is notpreferred as it may induce permanent abnormalinvoluntary movements !ike hemiballism anddyskinesia (3). Bilateral lesioning of the STN, whichare bordered by the corticobulbar and corticospinaltracts, theoretically has high potential to induce apseudobulbar syndrome.

The STN have three anatomical characteristicsthat make them difficult to loca!ize: small

dimensions, biconvex lens shape, and obliquity.Because the clinical benefit of STN stimulation is

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Turkish Neiirosiirgery 11: 1 - 8, 2001

entirely dependent on the accuracy of targetdetermination, MRI and electrophysiologicalguidance are used simultaneously for targeting O).Unilateral STN stimulation mainly affects thecontralateral hemibody (13,29). A patient withunilateral STN stimulation will continue to requireanti-parkinsonian medication for the ipsilateralhemibody. In advanced-stage disease, unilateralstimulation will not sufficiently improve gaitproblem s, and bilateral contemporaneous STNsurgery is preferred.

The effects of high-frequency DBS in the STNwere reviewed by Benabid et aL.(3). These authorsdemonstrated that bilateral stimulation of the STN

greatly improves off-period symptoms in this groupof severely disabled patients. Motor fluctuationswere attenuated, and patients with sudden on-oHfluctuations before surgery had milder fluctuationsthereafter. All patients became independent in mostactivities of daily living, and medications weredecreased to approximately half of the initial dosageafter the surgery. The three cardinal symptoms ofPO (bradykinesia, rigidity, and tremor) weredecreased by stimulation of the STN when patientswere off the medication. Off-medication and off­

stimulation Unified Parkinson' s Disease Rating Scale(UPDRS) motor sub-scale scores were also improved.This could be related either to the

microsubthalamotomy effect due to the presence ofthe stimulating electrode in the STN, or to along-Iasting inhibitory effect of chronic stimulation(29). •

A double-blind study done by Kumar andLozano yielded similar results (26). They reportedan approximately 65% reduction in off-periodparkinsonism, 40% improvement in on-periodparkinsonism, and 85% reduction in levodopa­induced dyskinesias. Although on-period functionswere also improved, the authors could not say withcertainty that parkinsonian features refractory to thesuprathreshold dose of levodopa would respond toSTN DBS. When patients who had undergonebilateral STN DBS were compared with those whohad undergone bilateral GPi DBS, the STN patientsshowed considerably greater improvement in off­period parkinsonism. In contrast to most reports onunilateral pallidotomy, bilateral STN DBS patientswere also significantly improved in on-period s (26).There are also reports about the effects of GPiand STN stimulation that favor the STN target in

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Berk: 511rgery for Pnrkiiisoii 's disense

young-onset PO with severe L-dopa-inducedmotor complications (25). STN DBS is alsoreported to significantly decrease parkinsoniantremor (37).

CONCLUSION

DBS is a powerful new tool in the treatment ofmovement disorders. it has become a standardtreatment for PO and essential tremor, and theapplications continue to expand as successful resultsare reported for other conditions. There is still debateabout whether DBS is actually superior to lesioning;however, the ease and benefits associated withadjustable parameters, and the added plus ofavoiding another lesion in an aIready sick brain seemto favor DBS more and more every day. We believethat the most important advantage of DBS is theability to titrate the effects to suit an individual' schanging symptoms.

Correspondence: Cagi ar Berk, MDDivision of Neurosurgery,University of British ColumbiaSuite 325, 700 West 10th Avenue,Vancouver, BC, Canada, V5Z 4E5Phone: 1-604-875 5894Fax: 1-604-875 4882

e-mail: caglarberk@hotmai1.com

REFERENCES

1. Bejjani BP, Dormont D, Pidioux B, Yelnik J, Damier P,Amulf I, Bonnet AM, Marsault C, Agid Y, Phillippon J,Cornu P: Bilateral subthalamic stimulation forParkinson' s disease by us ing three-dimensionalstereotactic magnetic resonance imaging andelectrophysi1ogical guidance. J Neurosurg 92: 615-625,2000

2. Bejjani B, Damier P, Amulf I, Bonnet AM, Vidailhet M,Dormont D, Pidoux B, Comu P, Marsault C, Agid Y:Pallidal stimuIation for Parkinson' s disease. Two targets?Neurology 49: 1564-1569, 1997

3. Benabid AL, Benazzouz A, Limousin P, Koudsie A,Krack P, Pollak P: Dyskinesias and the subthalamicnuc1eus. Ann Neurol Suppl1. 47: 189-192,2000

4. Benabid AL, Pollak P, Gao D, Hoffmann D, Limousin P,Gay E, Payen I, Benazzouz A: Chronic electricalstimulation of the ventralis intermedius nuc1eus ofthalamus as a treatment of movement disorders. JNeurosurg 84: 203-214, 1996

5. Benabid AL, Pollak P, Louveau A, Henry S, deRougemontJ: Combined (thalamotomy and stimulation)stereotactic surgery of the VIM thalamic nuc1eus forbilateral Parkinson's disease. Appl Neurophysiol50: 344­346, 1987

Tiirkis/i Neiirosiirgery 11: 1 - 8, 2001

6. Bertrand c: A pneumotaxic technique for producinglocalised cerebral lesions and its use in the treatment of

Parkinson's disease. J Neurosurg 15: 251-264, 1958

7. Bjorklund A, Lindvall O: Dopamine in dendrites of thesubstantia nigra neurons: Suggestions for a role indendritic terminals. Brain Res 83: 531-537, 1975

8. Browder J: Parkinsonism: Is it a surgical problem? NYState J Med 47: 2589-2592, 1947

9. Caparros-Lefebvre D, Blond S, Feltin MP, Pollak P,Benabid AL: Improvement of levodopa-induceddyskinesias by thalamic deep brain stimulation is relatedto slight variation in electrode placement: possibleinvolvement of centre median and parafaseicularis

complex. J Neurol Neurosurg Psychiatry 67: 308-314,1999

10. Caparros-Lefebvre D, Blond S, Vermersch P, PecheuxN, Guieu JD: Chronic thalamic stimulation improvestremor and levodopa-induced dyskinesias inParkinson' s disease. J Neurol Neurosurg Psychiatry 56:268-273, 1993

11. Cooper is: Ligation of anterior choroidal artery forinvoluntary movements-parkinsonism. PsychiatricQuart 27: 317-319,1953

12. Cotzias GC, Van Woert HM, Schiffer LM: Aromatic

amino acid s and modification of parkinsonism. N Eng JMed 276: 374-379, 1967

13. Damier P, Demeret S, Bejjani BP, Arnulf I, Gervais D,Agid Y: Does unilateral subthalamic stimulation onlyimprove contralateral parkinsonian signs? (abstract).Neurology Suppl 2. 52 :A272, 1999

14. Durif F, Lemaire JJ, Debil!y B, Dordain G: Acute andchronic effects of anteromedial globus pallidusstimulation in Parkinson's disease. J Neurol NeurosurgPsychiatry 67: 315-321, 1999

15. Fenelon F: Essais de traitement neurochirurgical dusyndrome parkinsonien par intervention directe sur lesvoies extrapyramidales immediatement sous­striopallidales (an sa lenticulare): Communication suiviede projection du film d'un des operes pris avant et apresl'intervention. Rev Neurol83: 437-440, 1950

16. Galvez-Jimenez N, Lozano A, Tasker R, Duff J,

Hutchinson W, Lang AE: Pallidal stimulation inParkinson' s disease patients with a prior unilateralpallidotomy. Can J Neurol Sci 25: 300-305, 1998

17. Ghika J, Vil!emure JG, Frankhauser H, Favre J, Assal G,

Ghika-Schmid F: Effieiency and safety of bilateralcontemporaneous pallidal stimulation (deep brainstimulation) in levodopa-responsive patients withParkinson's disease with severe motor fluctuations: a 2­

year follow-up review. J Neurosurg 89: 713-718, 199818. Gil! SS, Heywood P: Bilateral subthalamic nucleotomy

for advanced Parkinson's disease (letter). Lancet350:1224, 1997

19. Guiot G, Brion S: Traitement des mouvements anormaux

par la coagulation pallidale: Technique et resultats. RevNeurol89: 578-580, 1953

20. Guridi J, Obeso JA: The role of the subthalamic nucleus

in the origin of hemiballism and parkinsonism: new

Berk: Siirgery for Parkiiisoii's disease

surgical perspectives, in: Obeso JA, DeLong MR, OhyeC, Marsden CD (ed s) The basa 1ganglia and new surgicalapproaches for Parkinson's disease. Advances inNeurology, Vol 74, Philadelphia: Lipincott-Raven; 1997:235-247

21. Hamby WB: Parkinsonism: Is it a surgical problem?(comment) NY State J Med 47: 2592, 1947

22- Hassler R, Riechert T: Indika tionen und

Lokalisationsmethode der gezielten Hirnoperationen.Nervenartz 25: 441-447, 1954

23. Hornykiewicz O, Kish SJ: Biochemical pathophysiologyof Parkinson's disease. Adv NeuroI45:19-34, 1986

24. Jankovic J, Cardoso F, Grossman RG, Hamilton WJ:

Outcome af ter stereotactic thalamotomy forparkinsonian, essential, and other types of tremOLNeurosurgery 37: 680-687, 1995

25. Krack P, Pollak P, Limousin P, Hoffmann D, Xie J,Benazzouz A, Benabid AL: Subthalamic nucleus

stimulation or internal pallidal stimulation in youngonset Parkinson' s disease. Brain 121: 451-457, 1998

26. Kumar R, Lozano AM, Kim YJ, Hutchinson WD, Sime

E, Halket E, Lang AE: Double-blind evaluation ofsubthalamic nucleus deep brain stimulation in advancedParkinson's disease. Neurology 51: 850-855, 1998

27. Laitinen LV, Bergenheim T, Hariz MI: Leksell'sposteroventral pallidotomy in the treatment ofParkinson's disease. J Neurosurg 76: 53-61, 1992

28. Limousin P, Speelman JD, Gielen F, Janssens M:Multicentre European study of thalamic stimulation inparkinsonian and essential tremoL J Neurol NeurosurgPsychiatry 66: 289-296, 1999

29. Limousin P, Krack Pi Pollak P, Benazzouz A, ArdouinC, Hoffmann D, Benabid AL: Electrical stimulation ofthe subthalamic nucleus in advanced Parkinson's

disease. N Engl J Med 339: 1105-1111, 199830. Marsden CDi Obeso JA: The functions of the basal

ganglia and the paradox of stereotaxic surgery inParkinson's disease. Brain 117: 877-897, 1994

31. Meiback RC, Katzman R: Catecholaminergic innervationof the subthalamic nucleus: Evidence for a rostral

continuation of the A9 (substantia nigra) dopaminergiccell group. Brain Res 173: 364-368, 1979

32. Meyers R: Parkinsonismi athetosis and ballism: Areportof progress in surgical therapy. Postgrad Med 17: 369­381, 1955

33. Meyers R: Surgical procedure for postencephalitictremori with notes on the physiology of premotor fibers.Arch Neurol Psychiatry 44: 455-459, 1940

34. Mundinger F: Subthalamotomy in the treatment ofextrapyramidal motor disorders. Germ Med Meth 10:440-443, 1965

35. Narabayashi H, Okuma T: Procaine oil blocking of ofthe globus pallidus for the treatment of rigidity andtremor of parkinsonism. Proc Jpn Acad 29: 134-137, 1953

36. Ondo W, Jankovic Ji Schwartz Ki Almaguer Mi SimpsonRK: Unilateral thalamic deep brain stimulation forrefractory essential tremor and Parkinson's diseasetremor. Neurology 51: 1063-1069, 1998

37. Rodriguez MCi Guridi OJ, Alvarez Li Mewes Ki Macias

7

Tiirkis/i Neiirosiirgery 11: 1 - 8, 2001

R,VitekJ, Delon MR, Obeso JA:The subthalamic nucleusand tremor in Parkinson' s disease. Mov Disord 13: 111­118, 1998

38. Siegfried J, Wellis G: Chronic electrostimulation ofventroposterolateral pallidum: follow-up. ActaNeurochir Suppl. 68: 11-13,1997

39. Siegfried J, Lippitz B: Bilateral chronic stimulation ofventroposterolateral palIidum: a new therapeuticapproach for alleviating all parkinsonian symptoms.Neurosurgery 35: 1126-1130,1994

40. Siegfried J, Lippitz B: Chronic electrical stimulation ofthe VL-VPL complex and of the palIidum in thetreatment of movement disorders: Personal experiencesince 1982. Stereotact Funct Neurosurg 62: 71-75, 1994

41. Speelman JD, Schuurman PR, Bosch DA: Thalamicstimulation versus thalamotomy in a prospectiverandomized trial. Mov Disord Suppl2. 13: 200, 1998

42. Spiegel EA: Methodological problems onstereoencephalotomy. Confin Neurol26: 125-132, 1965

43. Spiegel EA, Wycis HT: Pallidothalamotomy in chorea.Arch Neurol Pyschiatry 64: 295-296, 1950

44. Starr PA, Vitek J, Bakay AE: Ablative surgery and deepbrain stimulation for Parkinson' s disease. Neurosurgery

8

Berk: Siirgen) for Parkiiisoii 's disease

43: 989-1015, 199945. Taha JM, Janszen MA, Favre J: Thalamic deep brain

stimulation for the treatment of head, voice, and bilaterallimb tremor. J Neurosurg 91: 68-72, 1999

46. Tasker RR: Deep brain stimulation is preferable tothalamotomy for tremor suppression. Surg Neurol 49:145-154, 1998

47. Tasker RR, Munz M, Junn FSCK, Kiss ZHT, Davis K,Dostrovsky JO, Lozano AM: Deep brain stimulation andthalamotomy for tremor compared. Acta NeurochirSuppl. 68: 49-53, 1997

48. Tasker RR, Organ LW, Hawrylyshyn P: Investigationof the surgical target for al1eviation of involuntarymovement disorders. Appl Neurophysiol45: 261-274,1982

49. Tronnier VN, Fogel W, Kroenenbuerger M, SteinvorthS: Pallidal stimulation: an alternative to pallidotomy?J Neurosurg 87: 700-705, 1997

50. Volkmann J, Sturm V, WeissP, Kappler J, Voges J,Koulousakis A, Lehrke R, Hefter H, Freund HJ:Bilateral high-frequency stimulation of the globuspallidus in advanced Parkinson's disease. Ann Neurol44: 953-961, 1998