Since Laitinen s report of pallidotomy for the treatment of advanced Parkinson s disease less

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1 i32 * SURGERY FOR MOVEMENT DISORDERS HISTORY Correspondene to: Dr Ralph Gregory, Oxford Movement Disorder Group, Radliffe Infirmary, Oxford OX2 6HE, UK; ralphgregory@ompuserve.om Ralph Gregory Sine Laitinen s report of pallidotomy for the treatment of advaned Parkinson s disease less than a deade ago, there has been a resurgene of interest in funtional neurosurgery for movement disorders. The onvergene of several paths, inluding the linial problem of levodopa indued dyskinesias and motor flutuations, inreased understanding of ellular pathophysiology, improved brain imaging and miroeletrode reording tehniques, and the development of deep brain stimulation (DBS), have paved the way for novel therapeuti strategies and major advanes in the field. The neurologist must work in partnership with the neurosurgeon in a multidisiplinary team, helping to optimise patient seletion, assess patients interoperatively, and supervise drug treatment and stimulation parameters postoperatively. OF MOVEMENT DISORDER SURGERY J Neurol Neurosurg Psyhiatry 2002;72(Suppl I):i32 i36 Surgery for movement disorders is not new (fig 1). Before 1975, thalamotomies had been performed worldwide. The breakthrough in the development of human stereotati surgery ame in 1947 when Speigel and Wyis deided to use landmarks within the brain, rather than the skull. Their first patient had a pallidal lesion for Huntington s horea. Parkinsonism (inluding many postenephaliti ases) was treated with lesions in the thalamus, ansa lentiularis. and pallidum. In 1952, Cooper inadvertently interrupted the anterior horoidal artery in a patient with Parkinson s disease, and the patient awoke with resolution of tremor and no defiit despite infartion of the globus pallidus. This led to the pratie of injeting alohol into this area. Lesions in the thalamus more reliably abolished tremor, so that by the late 1950s this had beome the preferred target, and partiularly the ventrointermediate (Vim) nuleus. Following the introdution of levodopa in 1968, stereotati surgery for Parkinson s disease was hardly performed and interest in the field waned. The next 15 years saw inreasing numbers of Parkinson s disease patients with dyskinesias and motor flutuations and a surgial solution was revisited. Following abortive attempts with adrenal medulla grafts, Lindvall s group in Sweden reported the transplantation of fetal dopamine ells into the striatum, but this has remained an experimental proedure. In the late 1980s pallidotomy was revisited, and by the mid 1990s many groups had onfirmed its effetiveness, partiularly for alleviating levodopa indued dyskinesias. Expertise and onfidene in these tehniques were rekindled but onern remained regarding high ompliation rates, partiularly when bilateral lesions were required. Brie and MLellan in 1980 were the first to treat two patients with multiple slerosis indued intention tremor by fully implantable thalami stimulators. Experiene inreased and tehnology improved, and in 1993 Benebid reported stimulation of the subthalami nuleus (STN), whih improved almost all parkinsonian symptoms allowing substantial redution of dopaminergi mediation. PARKINSON S DISEASE Patient seletion Patients are often referred for surgery when their disease is very advaned and the degree of disability severe. Apart from tremor response, the suessful outome of surgery for Parkinson s disease is dependent upon the presene of dopaminergi responsive symptoms to be effetive. Burned out ases, with no useful on periods, will not respond to surgery; similarly non-dopa responsive parkinsonian diseases, suh as multiple system atrophy, will not signifiantly benefit from surgery. The demographis of the ideal patient are listed in table 1. It is ruial that patients with signifiant ognitive or psyhiatri diffiulties are avoided. Drug indued halluinosis is a poor prognosti sign, and surgery would not be reommended as a way of trying to redue mediation. Those with postural instability and dysphonia, partiularly in the on state, do badly. The temptation is to offer surgery beause nothing more an be done, but this often leads to disaster. In my view, all pratial medial alternatives should have been tried. If an apomorphine servie is available, then this is a preferable option in the first instane. Surgery is assoiated with at least a 3% risk of signifiant permanent morbidity even in the best hands. Some patients prefer to onsider J Neurol Neurosurg Psyhiatry: first published as /jnnp.72.suppl_1.i32 on 1 Marh Downloaded from on 7 June 2018 by guest. Proteted by opyright.

2 NEUROLOGY IN PRACTICE Cortial Exlusion operations of Buy Klemme Int. Capsule Browder Basa Ganglia operations of Meyers Spiegel & Wyis Fenelon Guiot Cooper Pendunle Walker Figure 1 Spinal Cord Pyramidotomy Putnam Posterior Roots Sympatheti Chain Surgial targets for parkinsonism. surgery without a trial of mediation, despite thorough ounselling. This may be appropriate for tremor predominant disease (partiularly benign tremulous Parkinson s disease), but for other types, the trade off between side effets and effiay is not suffiiently favourable to reommend surgery early in the ourse of the disease. Surgial tehnique Target loation primarily relies on imaging for initial loalisation. Most groups now use magneti resonane imaging, but some rely solely on omputed tomographi sanning and oasionally ventriulography. The latter allows on table verifiation of anatomial loalisation, but adds to patient distress. The stereotati frame (fig 2) is usually fitted under general anaestheti, but the patient is woken up to allow linial onfirmation of symptom effetiveness and side effets. Patients without signifiant tremor or rigidity in the off state an be diffiult to assess intraoperatively. Bradykinesia does not respond rapidly to stimulation (table 2), and therefore annot be reliably used. Many groups use miroeletrode reording to Table 1 Ideal patient for pallidal or subthalami nuleus surgery Biologial age less than 70 years UPDRS off motor sore 40 80/108 Suprathreshold dose levodopa improves sore by 50% Severe drug indued dyskinesias (pallidal surgery) No falls when on (pull test) MMSE >24/30 Good bulbar funtion (partiularly in on state) No signifiant depression No drug indued halluinosis or other signifiant psyhoti symptoms MMSE, mini-mental state examination; UPDRS, unified Parkinson s disease rating sale. Figure 2 Intraoperative eletrode reording. map out the various nulei neurophysiologially. This an add onsiderably to the length of the surgial proedure, whih in some entres with the best published outomes often take more than 12 hours. On stimulation or lesioning of the pallidum or STN, transient dyskinesias may ensue, whih are usually a preditor of suessful outome. Overall the proedure is remarkably well tolerated. Lesions or stimulation High frequeny eletrial DBS provides an adjustable inhibitory effet on the target site, but at inreased ost (table 3). An aurately plaed lesion in the thalamus or pallidum provides reliable long lasting suppression of tremor and dyskinesias respetively, with no adverse effets. Bilateral lesions are invariably assoiated with adverse ognitive and bulbar effets, even when well plaed, and stimulation is therefore preferable in this situation. Lesioning of the STN is tehnially demanding beause of its small size, but benefits appear to be temporary and therefore stimulation of this target is now reommended. Though effetive, DBS requires areful postoperative adjustment that often takes many hours, and the replaement of equipment when hardware failure ours. In some series up to 20% of wires move, break, or beome infeted. The stimulation battery unit requires replaement every five years for STN stimulation, and three years for pallidal stimulation. Thalamus The thalamus is the final ommon outflow pathway for all tremors. Contralateral tremor is reliably suppressed with a lesion in the Vim nuleus and rigidity in the ventralis oralis posterior (Vop) nuleus. There is no effet on bradykinesia and although dyskinesia is oasionally helped, this is not a reliable observation. Even patients with tremor predominant Parkinson s disease will eventually develop bradykinesia in time, so it is now reommended that suh patients should have STN stimulation, rather than a thalami lesion or stimulation. Thalami lesional surgery should therefore be reserved for non-parkinson s disease tremor only (see below). Table 2 Differing latenies* of stimulation effets on symptoms Rigidity Tremor Bradykinesia Dyskinesias *Same latenies apply in reverse. Seonds Seonds to months Seonds to days Depends on redution of drugs and inrease in stimulation *i33 J Neurol Neurosurg Psyhiatry: first published as /jnnp.72.suppl_1.i32 on 1 Marh Downloaded from on 7 June 2018 by guest. Proteted by opyright.

3 i34 * Abbreviations DBS: deep brain stimulation STN: subthalami nuleus Vim: ventrointermediate Vop: ventralis oralis posterior Pallidum Posteroventral pallidal lesion or stimulation will reliably abolish ontralateral dyskinesias. This inludes biphasi and peak dose, and off state dystonias. Following optimal lesioning, the benefit an persist for at least five years. The improvement in off state bradykinesia also persists, but any improvement in on state dissipates after six months. Contralateral tremor may also be improved but this is not a reliable effet. Mediation remains unaltered following the proedure. Axial symptoms, inluding dyskinesias, do not improve, and non-dopaminergi gait and bulbar funtion are also not helped. On state postural instability and freezing may be worsened. Bilateral pallidotomy requires preise targeting, often with a smaller lesion on the less symptomati side to minimise adverse effets. Contralateral stimulation is now preferred to lesioning to avoid frontal exeutive defiits. Other potential side effets inlude visual field defets (opti trat), hemiparesis and dysarthria (internal apsule), and haemorrhage whih an be life threatening (5% mortality rate in some Table 3 Advantages Advantages and disadvantages of deep brain stimulation (DBS) DBS avoids destrutive brain lesion Stimulation parameters an be adjusted to optimise benefits and adverse effets DBS an be performed bilaterally with relative safety DBS does not prelude the use of future restorative surgial tehniques. Tramor redution, akinesia remains series). Delayed small vessel ipsilateral strokes (up to six months) are oasionally seen for reasons that are not lear. Weight gain, probably aused by redution in dyskinesias, is frequently observed. Subthalamus Bilateral subthalami stimulation alleviates all the ardinal symptoms of Parkinson s disease and benefits are preserved for more than five years. Unlike pallidal surgery, mediation an be redued by at least half postoperatively, and this leads to a redution in drug indued dyskinesias. Unilateral surgery an be offered to patients with very asymmetri disease, but most require bilateral surgery to avoid problems with variable mediation requirements on the two sides. Compliations an be transient or permanent (fig 3) and tolerane may develop to some (table 4). Dramati rebound symptoms an be seen following aute stimulator failure, sometimes neessitating emergeny admission. The reent stimulator units are less sensitive to eletromagneti interferene, suh as from light swithes and eletri motors. Patients are now usually given ontrol devies that an be preset to alter the stimulation parameters at home. Although the results in well seleted patients an be dramati and well maintained, STN stimulation requires onsiderable long term ommitment from the team looking after the patient. It has been estimated that eah patient requires on average 40 hours of adjustment for optimum benefit and maintenane of effet. For this reason, it Disadvantages NEUROLOGY IN PRACTICE Adverse events relating to proedure and implanted equipment. Battery life restrited to 2 5 years Cost of system and manpower Figure 3 Adverse effets of subthalami nuleus stimulation. J Neurol Neurosurg Psyhiatry: first published as /jnnp.72.suppl_1.i32 on 1 Marh Downloaded from Diplopia, fusion disturbanes, mydriasis, postural instability Inhibition of L-dopa effet, inreased akinesia Dystonia tetani, ontrations, dysarthria on 7 June 2018 by guest. Proteted by opyright.

4 NEUROLOGY IN PRACTICE Table 4 Habituation of stimulation indued adverse effets Dyskinesias Oular deviation Sensory mispereption Flushing (ipsilateral) Eyelid apraxia Musle ontrations Dysarthria/dysphonia Worsening akinesia Days to months Days to weeks Minutes to days Minutes to days Almost none is diffiult to envisage this proedure beoming widely available, unless there is a substantial inrease in the number of experiened staff in the units offering this servie. There is also onern about the frequeny of psyhiatri side effets, partiularly depression that probably arises as a result of the inhibition of STN limbi areas. The rate of suiide has been high in some series, whih is rarely seen with surgery to other targets. Patients with a history of signifiant depression should not be offered STN surgery. NON-PARKINSONIAN TREMOR Essential tremor A thalami Vim lesion will reliably suppress ontralateral tremor. Given the bilateral nature of the ondition, bilateral thalami stimulation is now the preferred option. Side effets are similar to those seen in pallidal surgery. Multiple slerosis tremor Careful patient seletion is ruial for a suessful outome, and only a small perentage of patients will benefit long term. Titubation will not improve, and pure upper limb tremor with little or no underlying dysmetria does best. This an often be diffiult to determine linially and we use visually guided wrist traking to identify those patients with single frequeny tremor. Patients with underlying pyramidal or sensory defiits in the tremulous limb will not be funtionally improved. Those with ognitive defiits are often worsened. We over the proedure with methylprednisolone in an attempt to redue the possibility of surgery induing a relapse. Distal tremor responds to targeting the thalamus (Vop) and proximal tremor the zona inerta. DYSTONIA AND OTHER MOVEMENT DISORDERS Improving tehniques and inreasing onfidene in funtional neurosurgery for Parkinson s disease has led to the study one more of its role in the treatment of other movement disorders, suh as dystonia, horea, and tardive dyskinesia. Thalamotomy has been the traditional target for dystonia, but the pallidum is now reognised as the preferred target. Bilateral pallidotomy has a dramati effet on idiopathi torsion dystonia inluding DYT 1, but the effets wane over several years. Bilateral pallidal DBS is now the favoured tehnique, and benefits appear to be maintained. Even botulinum resistant spasmodi tortiollis has been suessfully ontrolled with bilateral pallidal DBS and may replae seletive ervial denervation. Patients with seondary dystonia, suh as following head injury or stroke, experiene more modest improvements. Intraoperative stimulation in the awake state annot be performed, so the proedure relies heavily on imaging and miroeletrode tehniques for loalisation. Benefits also take several weeks and sometimes months to our. Pallidal stimulation requires higher voltages, pulse widths, and frequenies than STN and thalami targets, and sometimes benefits are only seen with parameters that require battery replaement every 18 months. SUMMARY There an be no doubt that funtional neurosurgery an produe dramati benefits, with a relatively small risk of adverse effets in experiened hands. Most groups now favour DBS to lesion therapy, but there remains a plae for palliative thalamotomy or pallidotomy in ertain situations. The vast majority of published series have been open label, not always onseutive, and on young, highly seleted patients. There must be onerns about publiation bias in favour of suessful outomes. Randomised omparative trials are few and are urgently required. There needs to be an emphasis on quality of life and ost effetiveness measures to justify the high initial and long term osts of these proedures. The hope must be that restorative surgery will replae the need for this tehnique, partiularly for Parkinson s disease. KEY REFERENCES 1 Gabriel EM, Nashold BS. Evolution of neuroablative surgery for involuntary movement disorders: an historial review. Neurosurgery 1999;42: An interesting and informative story that puts urrent day surgial pratie into perspetive. 2 Lozano AM, ed. Movement disorder surgery. Progress in neurologial surgery, vol 15. Basle; Karger, Overview of movement disorder surgery inluding pathophysiology. Exellent referene soure. 3 Laitinen LV, Bergenheim AT, Hariz MI. Leksell s posteroventral pallidotomy in the treatment of Parkinson s disease. J Neurosurg 1992;76: First landmark publiation reporting the suessful use of pallidotomy in the modern era. 4 De Bie RMA, de Haan RJ, Nijssen PCG, et al. Unilateral pallidotomy in Parkinson s disease: a randomised, single-blind, multientre trial. Lanet 1999;354: Only published randomised ontrolled trial of pallidotomy in peer reviewed journal. 5 Hariz MI, Bergenheim AT. A 10-year follow-up review of patients who underwent Leksell s posteroventral pallidotomy for Parkinson disease. J Neurosurg 2001;94: Confirmation of longterm ontralateral dyskinesia ontrol following pallidotomy for Parkinson s disease. 6 Gross RE, Lozano AM. Advanes in neurostimulation for movement disorders. Neurologial Researh 2000;22: Review of deep brain stimulation for various movement disorders. 7 Limousin P, Krak P, Pollak P, et al. Eletrial stimulation of the subthalami nuleus in advaned Parkinson s disease. N Engl J Med 1998;339: Review of STN stimulation, by Professor Benabid s group in Grenoble. 8 Volkmann J, Allert N, Voges J, et al. Safety and effiay of pallidal or subthalami nuleus stimulation in advaned PD. Neurology 2001; 56: Diret omparison (non-randomised) of STN and Gpi stimulation in Parkinson s disease. 9 Alusi SH, Aziz TZ, Glikman S, et al. Stereotati lesional surgery for the treatment of tremor in multiple slerosis: a prospetive ase-ontrolled study. Brain 2001;124: Provides good overview of the ritial importane of patient seletion for tremor surgery in multiple slerosis. 10 Adler CH, Kumar R. Pharmaologial and surgial options for the treatment of ervial dystonia. Neurology 2000;55(suppl 5):S9 14. Helpful overview of the medial and surgial treatments for spasmodi tortiollis. 11 Guridi J, Obeso JA. The subthalami nuleus, hemiballismus and Parkinson s disease: reappraisal of a neurosurgial dogma. Brain 2001;124:5 19. Disussion of why STN surgery in parkinsonian patients does not indue hemiballismus. *i35 J Neurol Neurosurg Psyhiatry: first published as /jnnp.72.suppl_1.i32 on 1 Marh Downloaded from on 7 June 2018 by guest. Proteted by opyright.

5 i36 * WORLD WIDE WEB... Surfing for movement disorders T he two major problems with searhing for any information on the internet on movement disorders (or indeed any other subjet) are that of data overload, and finding good quality information that is pithed at the orret level. WEMOVE is quite simply the most outstanding website on all subjets related to movement disorders. It avoids both of the above issues with high quality information that is appropriate for both a medial and lay audiene ( It inludes an extremely useful alert servie (EMOVE) whih sends updates of reent papers on a wide spetrum of movement disorder related topis or presentations from sientifi meetings (to register go to In addition there are slide sets whih are very useful for teahing I reently had to give a talk on Parkinson s disease at very short notie, and was able to put the entire talk together using their slides in less than two minutes! WEMOVE also links to many patient support web sites on Parkinson s disease, dystonia, essential tremor, and Wilson s disease to name but a few. Unfortunately many of these other sites are not that easy to navigate around, or don t provide partiularly useful information. However, two good examples are the Restless Legs Syndrome Foundation ( and the Virtual Hospital at University of Iowa with good patient information on Tourette s ( TouretteSyndrome.html). For a more UK based approah, a good starting point is the Glaxo Neurologial Centre at the Walton ( You will find links there to the Parkinson s Disease Soiety, Huntington s Disease Assoiation, MSA (Sarah Matheson Trust), PSP Soiety, Tourette s Assoiation, and many other UK based neurologial harities. It is perhaps a shame that there are not more sites whih use the potential advantages of the web to illustrate movement disorders with video, suh as on-off phenomena in Parkinson s disease or even some funtional neurosurgery (for example, tutorials/parkinsons/parkinsons2.html). Massahusetts General Hospital has a very useful site looking at funtional neurosurgery for Parkinson s disease, whih also has useful links inluding the unified Parkinson s disease (UPDRS) and Hoehn and Yahr rating sales ( In summary, if you are to visit one web site related to movement disorders it would have to be the WEMOVE site, whih also has the advantage of the most easy to remember web address ( Referene linking to full text of more than 200 journals Toll free links You an aess the FULL TEXT of artiles ited in the Journal of Neurology, Neurosurgery, and Psyhiatry online if the itation is to one of the more than 200 journals hosted by HighWire ( without a subsription to that journal. There are also diret links from referenes to the Medline abstrat for other titles. D Niholl Leiester Royal Infirmary d.j.niholl@bham.a.uk J Neurol Neurosurg Psyhiatry: first published as /jnnp.72.suppl_1.i32 on 1 Marh Downloaded from on 7 June 2018 by guest. Proteted by opyright.