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thalamuscoulddiminishtremor(Hassleretal.1960, Ohye et al. 1964). The idea of treating neurologic disorders with chronic stimulation began to emergein the 1960s, but stimulation was largely used for targeting surgical lesions (Bergstromet al. 1966). Sem-Jacobsen (1966) developeda method of implanting a bundle of multipleelectrode wires deep in the brain and leav-ing them in place for weeks, during whichstimulation could be delivered. The goal of the stimulation was to delineate the “best”target for a subsequent lesion. With the im-planted wires, a lesion could be made in smallsteps over a span of days to weeks to try to achieve maximum beneﬁt without unto- wardeffects.Althoughthegoalwasstilllesionguidance, this is perhaps the earliest reportof stimulation through chronically implantedelectrodes.Intheearly1970s,reportsofusingchronicstimulationtherapeuticallyemergedfortreat-ing pain (Hosobuchi et al. 1973), movementdisorders, or epilepsy (Cooper 1973). Cooperet al. (1976) published the ﬁrst large seriesof chronic cerebellar stimulation studies forcerebral palsy. In those cases, stimulation wasdelivered transcutaneously through inductivecoupling devices to electrodes implanted onthe surface of the cerebellar cortex. Beneﬁt was said to occur in 49 of 50 patients. How-ever, cerebellar stimulation in cerebral palsy eventuallyfelloutoffavorwhenblindedstud-ies failed to show consistent beneﬁts (Penn1982). By 1980, other reports of treatingmovementdisorderswithchronicstimulationhad appeared (Brice & McLellan 1980). Although the ﬁrst long-term internally implanted cardiac pacemaker was devel-oped by 1960, it was not until the 1990sthat implantable pacemaker technology wascombined with chronically implanted deepbrain electrodes for long-term chronic DBS(Benabid et al. 1991, 1996). Since then, DBShas become increasingly used for treating a variety of disorders. These are summarizedbrieﬂy in the section below.
internalsegment of theglobus pallidus
CLINICAL APPLICATIONS OF DEEP BRAIN STIMULATION Deep Brain Stimulation for Essential Tremor
TheﬁrstwidespreaduseofDBSintheUnitedStatesandEuropewasforthetreatmentofETor the tremor of PD. Benabid and colleagues(1991)ﬁrstreportedtheefﬁcacyofVIMstim-ulation with implantable pulse generators.Subsequently, they reported a larger series of patients with VIM stimulation for the treat-ment of tremor, with signiﬁcant beneﬁt inthe majority of patients (Benabid et al. 1996).Subsequent single and multicenter studieshave consistently reported substantial bene-ﬁtofVIMstimulationforETwithanaveragetremor reduction of over 80% in the majority of patients (Koller et al. 1999a, Ondo et al.1998, Rehncrona et al. 2003).
Deep Brain Stimulation for Parkinson Disease
Different sites of stimulation provide differ-ent clinical effects in PD. Thalamic stimu-lation in the region of the VIM may reducelimb tremor (Kumar et al. 2003, Putzke et al.2003) but has little effect on other manifes-tations of the disease (Benabid et al. 1996).Stimulation of the GPi may reduce all of themajor motor manifestations of PD, includingthereductionofdopa-induceddyskinesias,in- voluntary movements produced by individualdoses of dopaminergic medications that canlimittreatmentefﬁcacy(Andersonetal.2005,Peppe et al. 2001). GPi stimulation also may reduce painful cramps and sensory symptomsthat may occur when the beneﬁt from indi- vidual doses of levodopa abates (Loher et al.2002). However, GPi stimulation does nottypically permit the reduction of medication,and this may be a serious limitation for thosehaving drug-induced side effects such as or-thostasis, psychosis, daytime lethargy, or cog-nitive impairment. STN DBS provides sim-ilar reduction of motor symptoms (Benabid
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A n n u . R e v . N e u r o s c i . 2 0 0 6 . 2 9 . D o w n l o a d e d f r o m a r j o u r n a l s . a n n u a l r e v i e w s . o r g b y J O H N S H O P K I N S U N I V E R S I T Y o n 0 4 / 2 6 / 0 6 . F o r p e r s o n a l u s e o n l y .