Deep brain stimulation
370268
224400571
2008-07-08T18:09:10Z
AxelBoldt
2
/* Clinical depression */
In [[neurotechnology]], '''deep brain stimulation''' ('''DBS''') is a [[surgery|surgical]] treatment involving the implantation of a medical device called a [[brain pacemaker]], which sends electrical impulses to specific parts of the [[brain]]. DBS in select brain regions has provided remarkable therapeutic benefits for otherwise treatment-resistant movement and affective disorders such as [[chronic pain]], [[Parkinson’s disease]], [[tremor]] and [[dystonia]].<ref name=Kringelbach>Kringelbach ML, Jenkinson N, Owen SLF, Aziz TZ (2007). "Translational principles of deep brain stimulation". ''Nature Reviews Neuroscience''. 8:623–635. PMID 17637800.</ref> Despite the long history of DBS,<ref name=gildenberg>Gildenberg PL (2005). "Evolution of neuromodulation". ''Stereotact Funct Neurosurg'', 83(2–3), 71–79. PMID 16006778.</ref> its underlying principles and mechanisms are still not clear. DBS directly changes brain activity in a controlled manner, its effects are reversible (unlike those of lesioning techniques) and is one of only a few neurosurgical methods that allows [[Blind experiment|blinded studies]].
The [[Food and Drug Administration]] (FDA) approved DBS as a treatment for [[essential tremor]] in 1997, for [[Parkinson's disease]] in 2002,<ref name=USDHHS>U.S. Department of Health and Human Services.[http://www.fda.gov/bbs/topics/NEWS/NEW00580.html FDA approves implanted brain stimulator to control tremors.] Retrieved October 18, 2006.</ref> and [[dystonia]] in 2003.<ref> [http://knbc-tvhealth.ip2m.com/index.cfm?pt=itemDetail&item_id=97349&site_cat_id=470 'Brain pacemaker' treats dystonia.] KNBC TV, April 22, 2003. Retrieved October 18, 2006.</ref> DBS is also routinely used to treat [[chronic pain]] and has been used to treat various affective disorders, including [[clinical depression]]. While DBS has proven helpful for some patients, there is potential for serious complications and side effects.
==Components and placement==
The deep brain stimulation system consists of three components: the implanted pulse generator (IPG), the lead, and the extension. The IPG is a [[battery (electricity)|battery]]-powered neurostimulator encased in a titanium housing, which sends electrical pulses to the brain to interfere with [[neural]] [[action potential|activity]] at the target site. The lead is a coiled wire insulated in [[polyurethane]] with four [[platinum]] [[iridium]] electrodes and is placed in one of three areas of the brain. The lead is connected to the IPG by the extension, an insulated wire that runs from the head, down the side of the neck, behind the ear to the IPG, which is placed subcutaneously below the [[clavicle]] or in some cases, the [[Human abdomen|abdomen]].<ref name=NINDS>[[National Institute of Neurological Disorders and Stroke]]. [http://www.ninds.nih.gov/disorders/deep_brain_stimulation/deep_brain_stimulation.htm Deep brain stimulation for Parkinson's Disease information page.] Retrieved 23 November 2006.</ref> The IPG can be calibrated by a [[neurology|neurologist]], [[nurse]] or trained [[technician]] to optimize symptom suppression and control side effects.<ref name=Volkmann>Volkmann J, Herzog J, Kopper F, Deuschl G. "Introduction to the programming of deep brain stimulators". ''Mov Disord''. 2002 17, S181–187. PMID 11948775.</ref>
DBS leads are placed in the brain according to the type of symptoms to be addressed. For non-Parkinsonian [[essential tremor]] the lead is placed in the ventrointermedial nucleus (VIM) of the [[Human thalamus|thalamus]]. For [[dystonia]] and symptoms associated with [[Parkinson's disease]] ([[rigidity]], [[bradykinesia]]/[[akinesia]] and [[tremor]]), the lead may be placed in either the [[globus pallidus]] or [[subthalamic nucleus]].<ref>[http://www.surgeryencyclopedia.com/Ce-Fi/Deep-Brain-Stimulation.html Deep brain stimulation.] Surgery Encyclopedia. Retrieved January 25, 2007.</ref>
All three components are surgically implanted inside the body. Under local anesthesia, a hole about 14 mm in diameter is drilled in the skull and the electrode is inserted, with feedback from the patient for optimal placement. The installation of the IPG and lead occurs under general anesthesia.<ref>[http://www.neurosurgery.pitt.edu/imageguided/movement/stimulation.html Deep Brain Stimulation], Department of Neurological Surgery, University of Pittsburgh. Retrieved 13 May 2008.</ref> The right side of the brain is stimulated to address symptoms on the left side of the body and vice versa.
==Biochemistry==
It has been shown in [[thalamus|thalamic]] slices from mice,<ref>{{cite journal | author=Bekar L, Libionka W, Tian G, et al | title=Adenosine is crucial for deep brain stimulation–mediated attenuation of tremor| journal=Nature Medicine | year=2008 | pages=75–80 | volume=14 | issue=1 | doi=10.1038/nm1693}}</ref> that DBS causes nearby [[astrocyte]]s to release [[adenosine triphosphate]] (ATP), a precursor to [[adenosine]] (through a catabolic process). In turn, adenosine A1 receptor activation depresses excitatory transmission in the thalamus, thus causing an inhibitory effect that mimicks [[ablative brain surgery|ablation]] or "lesioning".
==Applications==
===Parkinson's disease===
[[Image:Parkinson surgery.jpg|thumb|250px|Insertion of electrode during surgery]]
[[Parkinson's disease]] (also known as paralysis agitans) is a [[neurodegenerative disease]] whose primary symptoms are [[tremor]], [[rigidity]], [[bradykinesia]] and postural instability.<ref>Ropper (2005), p. 916</ref> DBS does not cure Parkinson's, but it can help manage some of its symptoms and subsequently improve the patient’s [[quality of life]].<ref>Kleiner-Fisman G, Herzog J, Fisman DN, et al. "Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes." ''Mov Disord''. 2006 Jun;21 Suppl 14:S290–304 PMID 16892449</ref> At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications, or whose medications have severe side effects.<ref name=NINDS/> Its direct effect on the physiology of brain cells and [[neurotransmitters]] is currently debated, but by sending high frequency electrical impulses into specific areas of the brain it can mitigate symptoms<ref>Moro E, Lang AE. "Criteria for deep-brain stimulation in Parkinson's disease: review and analysis". ''Expert Review of Neurotherapeutics''. 2006 Nov;6(11):1695–705. PMID 17144783</ref> and/or directly diminish the side effects induced by Parkinsonian medications,<ref>Apetauerova D, Ryan RK, Ro SI, Arle J, et al. "End of day dyskinesia in advanced Parkinson's disease can be eliminated by bilateral subthalamic nucleus or globus pallidus deep brain stimulation". ''Movement Disorders''. 2006 Aug;21(8):1277–9. PMID 16637040 </ref> allowing a decrease in medications, or making a medication regimen more tolerable.
There are a few sites in the brain that can be targeted to achieve differing results, so each patient must be assessed individually, and a site will be chosen based on their needs. Traditionally, the two most common sites are the [[subthalamic nucleus]] (STN) and the [[globus pallidus interna]] (GPi), but other sites, such as the caudal [[zona incerta]] and the [[pallidofugal fibers]] medial to the STN, are being evaluated and showing promise.<ref>Plaha P, Ben-Shlomo Y, Patel NK, Gill SS. "Stimulation of the caudal zona incerta is superior to stimulation of the subthalamic nucleus in improving contralateral parkinsonism". ''Brain'' (2006). 129, 1732–1747 PMID 16720681</ref>
Research is being conducted as of 2007 to predict the onset of tremors before they occur by monitoring activity in the [[subthalamic nucleus]]. The goal is to provide stimulating pulses only when they are needed, to stop any tremors occurring before they start.<ref>[http://www.timesonline.co.uk/tol/life_and_style/health/article2079637.ece The blade runner generation.] ''The Sunday Times'', [[July 22]], [[2007]]. Retrieved on [[2008-03-20]].</ref>
DBS is approved in the United States by the Food and Drug Administration for the treatment of Parkinson's.<ref name=USDHHS/> DBS carries the risks of major surgery, with a complication rate related to the experience of the surgical team.
===Clinical depression===
Researchers reported in 2005 that electrical stimulation of a small area of the [[frontal cortex]] brought about a "striking and sustained remission" in four out of six patients suffering from [[clinical depression]]. Their symptoms had previously been resistant to [[medication]], [[psychotherapy]] and [[electroconvulsive therapy]].<ref name=Mayberg>Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (March 3, 2005). "Deep brain stimulation for treatment-resistant depression". ''Neuron''. 45(5):651–60. PMID 15748841.</ref>
Using [[neuroimaging|brain imaging]], the researchers had noticed that activity in the subgenual cingulate region (SCR or [[Brodmann area 25]])—the lowest part of a band of tissue that runs along the midline of the [[brain]]—seemed to correlate with symptoms of sadness and depression. They implanted electrodes into six patients while they were locally [[Anesthetic|anesthetised]], but alert. While the current was switched on, four of the patients reported feeling a black cloud lifting, and became more alert and interested in their [[social environment|environment]]s. The changes reversed when the current was switched off.<ref name=Mayberg/>
The effects of continuous SCR stimulation have produced sustained [[remission]] from depression in the four patients for six months. When reporting the results, the team did caution that the trial was so small that the findings must be considered only provisional.<ref name=Mayberg/>
Another hypothetically interesting site for DBS in depression is the [[nucleus accumbens]],<ref name=Schlaepfer>Schlaepfer TE, Lieb K. "Deep brain stimulation for treatment of refractory depression". ''Lancet''. 2005 Oct 22-28;366(9495):1420–2. PMID 16243078.</ref> as that region appears to be associated with pleasure and reward mechanisms. A 2007 study reported that experimental use of deep brain stimulation of the nucleus accumbens showed promising results, with patients suffering from profound depression reporting relief from their symptoms.<ref name=Schlaepfer2>Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V. "Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression". ''Neuropsychopharmacology''. 2007 Apr 11. PMID 17429407.</ref>
===Tourette syndrome===
Deep brain stimulation has been used experimentally in treating a few patients with severe [[Tourette syndrome]]. Despite widely publicized early successes, DBS remains a highly [[Biomedical research|experimental]] procedure for the treatment of Tourette's, and more study is needed to determine whether long-term benefits outweigh the risk.<ref>[[Tourette Syndrome Association]]. [http://web.archive.org/web/20051122154536/http://tsa-usa.org/news/DBS-Statement.htm Statement: Deep Brain Stimulation and Tourette Syndrome.] Retrieved [[November 22]] [[2005]].</ref> The procedure is well tolerated, but complications include "short battery life, abrupt symptom worsening upon cessation of stimulation, hypomanic or manic conversion, and the significant time and effort involved in optimizing stimulation parameters".<ref name=Malone>Malone DA Jr, Pandya MM (2006). "Behavioral neurosurgery". ''Adv Neurol.'' 99:241–7. PMID 16536372</ref> As of 2006, there were five published reports of DBS in patients with TS; all experienced reduction in tics and the disappearance of obsessive-compulsive behaviors. "Only patients with severe, debilitating, and treatment-refractory illness should be considered; while those with severe personality disorders and substance abuse problems should be excluded."<ref name=Malone/>
There may be serious short- and long-term risks associated with DBS in persons with head and neck [[tic]]s. The procedure is invasive and expensive, and requires long-term expert care. Benefits for severe Tourette's are not conclusive, considering less robust effects of this surgery seen in the [[Netherlands]]. Tourette's is more common in [[pediatric]] populations, tending to remit in adulthood, so this would not generally be a recommended procedure for use on children. Because diagnosis of Tourette's is made based on a history of symptoms rather than analysis of neurological activity, it may not always be clear how to apply DBS for a particular patient. Due to concern over the use of DBS in the [[treatment of Tourette syndrome]], the [[Tourette Syndrome Association]] convened a group of experts to develop recommendations guiding the use and potential [[clinical trials]] of DBS for TS.<ref>Mink JW, Walkup J, Frey KA, et al (November 2006). "Patient selection and assessment recommendations for deep brain stimulation in Tourette syndrome". ''Mov Disord.'' 21(11):1831–8. PMID 16991144</ref>
===Other clinical applications===
In August 2007, ''Nature'' reported that scientists in the US has successfully stimulated a 38-year-old man who had been in a minimally conscious state for six years using DBS.<ref>[http://www.nature.com/news/2007/070730/full/448522a.html Implant boosts activity in injured brain.] ''Nature'' news ([[1 August]] [[2007]]). Retrieved on [[2007-08-01]]</ref>
DBS has been used in the treatment of [[obsessive-compulsive disorder]]<ref>Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B (1999). "Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder". ''Lancet''. 1999 Oct 30;354(9189):1526 PMID 10551504</ref> and [[phantom limb pain]].<ref>Kringelbach, Morten L. et al. (2007). "Deep brain stimulation for chronic pain investigated with magnetoencephalography". ''Neuroreport'', 18(3), pp. 223–228.</ref> Although the clinical efficacy is not questioned, the mechanisms by which DBS works is still debated.<ref name=Benabid>Benabid AL, Wallace B, Mitrofanis J, Xia R, Piallat B, Chabardes S, Berger F. (2005). "A putative generalized model of the effects and mechanism of action of high frequency electrical stimulation of the central nervous system". ''Acta Neurol Belg''. 2005 Sep;105(3):149–57. PMID 16255153</ref> Long-term clinical observation has shown that the mechanism is not due to a progressive [[lesion]], given that interruption of stimulation reverses its effects.<ref name=Benabid/> Results of DBS in dystonia patients, where positive effects often appear gradually over a period of weeks to months, indicate a role of functional reorganization in at least some cases.<ref>{{cite journal | author = Krauss JK| title = Deep brain stimulation for dystonia in adults. Overview and developments| journal = Stereotactic and Functional Neurosurgery| volume = 78| issue = 3–4 | pages = 168–182 | year = 2002 | pmid = 12652041 | doi = 10.1159/000068963}}</ref> The procedure is being tested for effectiveness in patients with severe [[epilepsy]].<ref>Velasco F, Velasco M, Velasco AL, Jimenez F, Marquez I, Rise M (1995). "Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies". ''Epilepsia'' 36: 63–71. PMID 8001511</ref>
==Potential complications and side effects==
While DBS is helpful for some patients, there is also the potential for [[Neuropsychiatry|neuropsychiatric]] side effects. Reports in the literature describe the possibility of [[apathy]], [[hallucinations]], [[compulsive gambling]], [[hypersexuality]], [[Cognition|cognitive]] dysfunction, and [[Clinical depression|depression]]. However, these may be temporary and related to correct placement and calibration of the stimulator and so are potentially reversible.<ref>{{cite journal | author = Burn D, Troster A| title = Neuropsychiatric Complications of Medical and Surgical Therapies for Parkinson's Disease | journal = Journal of Geriatric Psychiatry and Neurology| volume = 17| issue = 3 | pages = 172–180 | year = 2004 | pmid = 15312281 | doi = 10.1177/0891988704267466}}</ref> A recent trial of 99 Parkinson's patients who had undergone DBS suggested a decline in [[executive system|executive functions]] relative to patients who had not undergone DBS, accompanied by problems with word generation, attention and learning. About 9% of patients had "psychiatric events", which ranged in severity from a relapse in [[voyeurism]] to a [[suicide]] attempt. Most patients in this trial reported an improvement in their quality of life following DBS, and there was an improvement in their physical functioning.<ref>{{cite journal | author = Smeding H, Speelman J, Koning-Haanstra M, et al| title = Neuropsychological effects of bilateral STN stimulation in Parkinson disease: A controlled study| journal = Neurology| volume = 66| issue = 12 | pages = 1830–1836 | year = 2006 | pmid = 16801645 | doi = 10.1212/01.wnl.0000234881.77830.66}}</ref>
Because the brain can shift slightly during surgery, there is the possibility that the electrodes can become displaced or dislodged. This may cause more profound complications such as personality changes, but electrode misplacement is relatively easy to identify using [[computed tomography|CT]] or [[MRI]]. There may also be complications of surgery, such as bleeding within the brain.
After surgery, swelling of the brain tissue, mild disorientation and sleepiness are normal. After 2–4 weeks, there is a follow-up to remove sutures, turn on the neurostimulator and program it.
==See also==
* [[Neurosurgery]]
* [[Stereotactic surgery]]
* [[Psychosurgery]]
* [[Neuroprosthetics]]
* [[Brain implant]]
* [[Vagus nerve stimulation]]
==Notes==
{{reflist|2}}
==References==
* Appleby BS, Duggan PS, Regenberg A, Rabins PV (2007). "Psychiatric and neuropsychiatric adverse events associated with deep brain stimulation: A meta-analysis of ten years' experience". ''Movement Disorders'' 22:1722–1728 PMID 17721929
* Bekar L, Libionka W, Tian G, Xu Q, Torres A, Wang X, Lovatt D, Williams E, Takano T, Schnermann J, Bakos R, Nedergaard M (2008). "Adenosine is crucial for deep brain stimulation–mediated attenuation of tremor". ''Nature Medicine'', v.14, n.1, pp.75–80.
* Fins JJ. Deep Brain Stimulation (2004) In, Encyclopedia of Bioethics, 3rd Edition. Post, SG, Editor-in-Chief. New York: MacMillan Reference. Volume 2, pp. 629–634.
* Gildenberg Philip L and Tasker, Ronald R (1998). ''Textbook of stereotactic and functional neurosurgery'', McGraw-Hill Publishing.
* Gildenberg Philip L (2005). "Evolution of neuromodulation". ''Stereotact Funct Neurosurg'', 83(2–3), 71–79. PMID 16006778
* Kringelbach ML, Jenkinson N, Owen SLF, Aziz TZ (2007). "Translational principles of deep brain stimulation". ''Nature Reviews Neuroscience''. 8:623–635. PMID 17637800
* McIntyre CC, Grill WM (2000). "Selective microstimulation of central nervous system neurons". ''Annals of Biomedical Engineering'' 38:219–233. PMID 10784087
* McIntyre CC, Grill WM, Sherman DL, Thakor NV (2004). "Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition". ''Journal of Neurophysiology'' 91:1457–1469. PMID 14668299
* Ropper Allan H and Brown, Robert H. (2005) ''Adams and Victor's Principles of Neurology (8th Edition)'', McGraw-Hill Medical Publishing. ISBN 007141620X
==External links==
*[http://www.med.ege.edu.tr/~norolbil/2001/NBD15501.html Deep brain stimulation for movement disorders]
[[Category:Neurosurgery]]
[[Category:Neurology]]
[[Category:Neuroprosthetics]]
[[Category:Tourette syndrome]]
[[de:Tiefe Hirnstimulation]]
[[hu:Mély agyi stimuláció]]
[[ja:脳深部刺激療法]]
[[nl:Diepe hersenstimulatie]]
[[no:Dyp hjernestimulasjon]]
[[tr:Derin beyin stimülasyonu]]