Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Standard view
Full view
of .
Look up keyword
Like this
0 of .
Results for:
No results containing your search query
P. 1
Deep Brain Stimulation

Deep Brain Stimulation

Ratings: (0)|Views: 241 |Likes:
Published by bajackson2

More info:

Published by: bajackson2 on Apr 27, 2009
Copyright:Attribution Non-commercial


Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less





 ANRV278-NE29-08 ARI 8 March 2006 11:33
Deep Brain Stimulation
 Joel S. Perlmutter
and Jonathan W. Mink 
Departments of Neurology, Radiology, Physical Therapy and Anatomy &Neurobiology, Washington University School of Medicine, Washington University inSt. Louis, St. Louis, Missouri 63110; email: joel@npg.wustl.edu
Departments of Neurology, Neurobiology & Anatomy, Brain & Cognitive Sciences,and Pediatrics, University of Rochester, Rochester, New York 14642;email: Jonathan Mink@urmc.rochester.edu Annu. Rev. Neurosci.2006. 29:229–57 The
Annual Review of   Neuroscience
is online atneuro.annualreviews.orgdoi: 10.1146/annurev.neuro.29.051605.112824Copyrightc
2006 by  Annual Reviews. All rightsreserved0147-006X/06/0721-0229$20.00
Key Words
movement disorders, Parkinson disease, dystonia, tremor,physiology 
Deep brain stimulation (DBS) has provided remarkable benefits forpeople with a variety of neurologic conditions. Stimulation of the ventralintermediatenucleusofthethalamuscandramaticallyrelievetremor associated with essential tremor or Parkinson disease (PD).Similarly,stimulationofthesubthalamicnucleusortheinternalseg-ment of the globus pallidus can substantially reduce bradykinesia,rigidity, tremor, and gait difficulties in people with PD. Multiplegroups are attempting to extend this mode of treatment to otherconditions. Yet, the precise mechanism of action of DBS remainsuncertain. Such studies have importance that extends beyond clini-cal therapeutics. Investigations of the mechanisms of action of DBShavethepotentialtoclarifyfundamentalissuessuchasthefunctionalanatomy of selected brain circuits and the relationship between ac-tivity in those circuits and behavior. Although we review relevantclinical issues, we emphasize the importance of current and futureinvestigations on these topics.
First published online as a Reviewin Advance on March 15, 2006
   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 .
 ANRV278-NE29-08 ARI 8 March 2006 11:33
INTRODUCTION................. 230HISTORY OF DEEP BRAINSTIMULATION ................ 230CLINICAL APPLICATIONS OFDEEP BRAINSTIMULATION ................ 231Deep Brain Stimulation forEssential Tremor.............. 231Deep Brain Stimulation forParkinson Disease............. 231Deep Brain Stimulation forDystonia...................... 232Deep Brain Stimulation for Tourette Syndrome............ 233Deep Brain Stimulation for Pain .. 233Deep Brain Stimulation forDepression and ObsessiveCompulsive Disorder.......... 233NEUROPHYSIOLOGY OF DEEPBRAIN STIMULATION ........ 234 Ventral Thalamic Nuclei.......... 235Synthesis of NeurophysiologicData.......................... 242FUNCTIONAL IMAGING OFDEEP BRAINSTIMULATION–INDUCEDCHANGES IN BRAINCIRCUITS...................... 244Positron Emission Tomography... 244Functional Magnetic ResonanceImaging Studies of Deep BrainStimulation ................... 246CONCLUSIONS................... 246
Deep brain stimulation (DBS) has provided
deep brainstimulation
essential tremor
ventralintermediate nucleusof the thalamus
dramatic clinical benefit for people with es-sential tremor (ET) and Parkinson disease(PD). Placement of high frequency stimulat-ing electrodes in the region of the ventral in-termediatenucleusofthethalamus(VIM)canmarkedly reduce tremor in these conditions,and stimulation of either the subthalamic nu-cleus (STN) or the internal segment of theglobus pallidus (GPi) may not only reducetremor, but also decrease bradykinesia, rigid-ity, and gait impairment that plague people with PD. Furthermore, many have touted thepotential benefit of DBS of selected brain re-gions for other movement disorders such asdystoniaorTourettesyndrome,aswellasava-rietyofdisorderssuchaspain,depression,andobsessive compulsive disorder (OCD). De-spite these realized and potential advances intreatment, controversy swirls around a num-berofclinicallyrelevantandbasicmechanisticissues.Whatconditionsareamenabletotreat-ment by DBS? What are the mechanisms of action of DBS? What effect does DBS haveon the function of brain circuits? We ad-dress these controversial issues and empha-size the need for future investigations. To setthe stage, however, we first review the history of the development of DBS as a therapeutictool.
Ever since Fritsch & Hitzig’s (1870) clas-sical demonstration of the localized electri-cal excitability of the motor cortex, electricalstimulation of the brain has played a majorrole in investigations of brain function. Thefirst report of human cortical stimulation ap-peared four years later (Bartholow 1874). Al-though electrical stimulation was used to mapcortical function in the 1930s (Penfield &Boldrey 1937), it was not until human stereo-taxic devices were developed that neuro-surgeons could begin to investigate the ef-fects ofstimulating deeper structures(Spiegelet al. 1947). By the early 1950s, intraoper-ative stimulation was used to identify deepstructures such as the corticospinal tract priorto lesioning the globus pallidus or thala-mus (Spiegel & Wycis 1952). Most reportsin the 1950s focused on positive phenomenathat were elicited by stimulation. In the early 1960s, it was reported that high-frequency (100-Hz) stimulation of the ventrolateral
230 Perlmutte
   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 .
 ANRV278-NE29-08 ARI 8 March 2006 11:33
thalamuscoulddiminishtremor(Hassleretal.1960, Ohye et al. 1964). The idea of treating neurologic disorders with chronic stimulation began to emergein the 1960s, but stimulation was largelused 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
 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
Deep Brain Stimulation 231
   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 .

Activity (3)

You've already reviewed this. Edit your review.
1 thousand reads
1 hundred reads
Gabriel Cooper liked this

You're Reading a Free Preview

/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->