Deep brain stimulation
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|Deep brain stimulation|
Deep brain stimulation (DBS) is a 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 therapeutic benefits for otherwise-treatment-resistant movement and affective disorders such as Parkinson's disease, essential tremor, dystonia, and chronic pain. Despite the long history of DBS, 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 it is one of only a few neurosurgical methods that allow blinded studies.
The Food and Drug Administration (FDA) approved DBS as a treatment for essential tremor in 1997, for Parkinson's disease in 2002, and dystonia in 2003. DBS is also used in research studies to treat chronic pain and has been used to treat various affective disorders, including major depression; neither of these applications of DBS have yet been FDA-approved. 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-powered neurostimulator encased in a titanium housing, which sends electrical pulses to the brain to interfere with neural 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 abdomen. The IPG can be calibrated by a neurologist, nurse, or trained technician to optimize symptom suppression and control side-effects.
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 ventrointermediate nucleus (VIM) of the 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 the subthalamic nucleus.
All three components are surgically implanted inside the body. Lead and extension implantation may take place under local anesthesia or with the patient under general anesthesia ("asleep DBS"). A hole about 14 mm in diameter is drilled in the skull and the electrode is inserted. During the awake procedure with local anesthesia, feedback from the patient is used to determine optimal placement. During the asleep procedure, intraoperative MRI guidance is used for direct visualization of brain tissue and device. The installation of the IPG and lead occurs under general anesthesia. The right side of the brain is stimulated to address symptoms on the left side of the body and vice versa.
Parkinson's disease is a neurodegenerative disease whose primary symptoms are tremor, rigidity, bradykinesia, and postural instability. DBS does not cure Parkinson's, but it can help manage some of its symptoms and subsequently improve the patient’s quality of life. At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications, or whose medications have severe side-effects. 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 and/or directly diminish the side-effects induced by Parkinsonian medications, 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.
DBS is approved in the United States by the Food and Drug Administration for the treatment of Parkinson's. DBS carries the risks of major surgery, with a complication rate related to the experience of the surgical team. The major complications include hemorrhage (1–2%) and infection (3–5%).
Stimulation of the periaqueductal gray and periventricular gray for nociceptive pain, and the internal capsule, ventral posterolateral nucleus, and ventral posteromedial nucleus for neuropathic pain has produced impressive results with some patients, but results vary and appropriate patient selection is important. One study of seventeen patients with intractable cancer pain found that thirteen were virtually pain-free and only four required opioid analgesics on release from hospital after the intervention. Most ultimately did resort to opioids, usually in the last few weeks of life. DBS has also been applied for phantom limb pain.
Deep brain stimulation has been used in a small number of clinical trials to treat patients suffering from a severe form of treatment-resistant depression (TRD). A number of neuroanatomical targets have been utilised for deep brain stimulation for TRD including the subgenual cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, inferior thalamic peduncle, and the lateral habenula. The small patient numbers in the early trials of deep brain stimulation for TRD currently limit the selection of an optimum neuroanatomical target. There is insufficient evidence to support DBS as a therapeutic modality for depression; however, the procedure may be an effective treatment modality in the future.
A systematic review of DBS for treatment-resistant depression and obsessive–compulsive disorder identified 23 cases—nine for OCD, seven for treatment-resistant depression, and one for both. It found that "about half the patients did show dramatic improvement" and that adverse events were "generally trivial" given the younger psychiatric patient population than with movements disorders.
DBS for treatment-resistant depression can be as effective as antidepressants, with good response and remission rates, but adverse effects and safety must be more fully evaluated. Common side-effects include "wound infection, perioperative headache, and worsening/irritable mood ... and ... increased suicidality".
Deep brain stimulation has been used experimentally in treating adults with severe Tourette syndrome that does not respond to conventional treatment. Despite widely publicized early successes, DBS remains a highly experimental procedure for the treatment of Tourette's, and more study is needed to determine whether long-term benefits outweigh the risks. 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". As of 2006, there were five reports in patients with TS; all experienced reduction in tics and the disappearance of obsessive-compulsive behaviors.
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 in general this would not 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.
Robertson reports that DBS had been used on 55 adults as of 2011, remains an experimental treatment, and "should only be conducted by experienced functional neurosurgeons operating in centres which also have a dedicated Tourette syndrome clinic". According to Malone et al (2006), "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." Du et al (2010) say that "As an invasive therapy, DBS is currently only advisable for severely affected, treatment-refractory TS adults". Singer (2011) says that "pending determination of patient selection criteria and the outcome of carefully controlled clinical trials, a cautious approach is recommended". Viswanathan A et al (2012) say that DBS should be used in patients with "severe functional impairment that can not be managed medically".
Other clinical applications
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.
The procedure has been tested for effectiveness in patients with severe epilepsy. A review of 189 studies covering DBS as well as vagus nerve stimulation and closed-loop stimulation (responsive neurostimulator [RNS]) indicate that neurostimulation provides "another tool with which to treat the complex disease of medically refractory epilepsy".
Potential complications and side effects
While DBS is helpful for some patients, there is also the potential for neuropsychiatric side-effects, including apathy, hallucinations, compulsive gambling, hypersexuality, cognitive dysfunction, and depression. However, these may be temporary and related to correct placement and calibration of the stimulator and so are potentially reversible.
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 CT. 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.
- Stereotactic surgery
- Brain implant
- Vagus nerve stimulation
- Electroconvulsive therapy
- Kringelbach ML, Jenkinson N, Owen SLF, Aziz TZ (2007). "Translational principles of deep brain stimulation". Nature Reviews Neuroscience. 8:623–635. PMID 17637800.
- Gildenberg PL (2005). "Evolution of neuromodulation". Stereotact Funct Neurosurg, 83(2–3), 71–79. PMID 16006778.
- Hammond C.,Ammari R, Bioulac B, Garcia L (2008) Latest view on the mechanism of action of deep brain stimulation. Mov Disord 23: 2111–21
- García MR, Pearlmutter BA, Wellstead PE, Middleton RH (2013). "A Slow Axon Antidromic Blockade Hypothesis for Tremor Reduction via Deep Brain Stimulation". PLoS ONE 8 (9): e73456. doi:10.1371/journal.pone.0073456.
- U.S. Department of Health and Human Services.FDA approves implanted brain stimulator to control tremors. Retrieved October 18, 2006.
- 'Brain pacemaker' treats dystonia. KNBC TV, April 22, 2003. Retrieved October 18, 2006.
- National Institute of Neurological Disorders and Stroke. Deep brain stimulation for Parkinson's Disease information page. Retrieved November 23, 2006.
- Volkmann J, Herzog J, Kopper F, Deuschl G. "Introduction to the programming of deep brain stimulators". Mov Disord. 2002 17, S181–187. PMID 11948775.
- Deep brain stimulation. Surgery Encyclopedia. Retrieved January 25, 2007.
- Starr PA, Martin AJ, Ostrem JL, Talke P, Levesque N, Larson PS. Subthalamic nucleus deep brain stimulator placement using high-field interventional magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy. J Neurosurg. 2010 Mar;112(3):479-90. doi: 10.3171/2009.6.JNS081161. PMID 19681683
- Deep Brain Stimulation, Department of Neurological Surgery, University of Pittsburgh. Retrieved May 13, 2008.
- Ropper (2005), p. 916
- 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
- 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
- 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
- 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
- Doshi PK. "Long-term surgical and hardware-related complications of deep brain stimulation". Stereotact Funct Neurosurg (2011). 89:2, 89–95. PMID 21293168
- Young RF & Brechner T. Electrical stimulation of the brain for relief of intractable pain due to cancer. Cancer. 1986;57:1266–72. PMID 3484665.
- Johnson MI, Oxberry SG & Robb K. Stimulation-induced analgesia. In: Sykes N, Bennett MI & Yuan C-S. Clinical pain management: Cancer pain. 2nd ed. London: Hodder Arnold; 2008. ISBN 978-0-340-94007-5. p. 235–250.
- Kringelbach, Morten L. et al. (2007). "Deep brain stimulation for chronic pain investigated with magnetoencephalography". Neuroreport, 18(3), pp. 223–228.
- Anderson, R. J., Frye, M. A., Abulseoud, O. A., Lee, K. H., McGillivray, J. A., Berk, M., & Tye, S. J. (2012). "Deep brain stimulation for treatment-resistant depression: Efficacy, safety and mechanisms of action". Neuroscience & Biobehavioral Reviews. 36(8), 1920–1933. PMID 22721950. http://dx.doi.org/10.1016/j.neubiorev.2012.06.001
- Curr Opin Psychiatry. 2009 May;22(3):306–11
- Lakhan SE, Callaway H. "Deep brain stimulation for obsessive-compulsive disorder and treatment-resistant depression: systematic review". BMC Research Notes. 2010 Mar 4;3(1):60. doi:10.1186/1756-0500-3-60 PMID 20202203
- Moreines JL, McClintock SM, Holtzheimer PE. "Neuropsychologic effects of neuromodulation techniques for treatment-resistant depression: a review". Brain Stimul. 2011 Jan;4(1):17-27. PMID 21255751
- Singer HS. "Tourette syndrome and other tic disorders". Handb Clin Neurol. 2011;100:641–57. doi:10.1016/B978-0-444-52014-2.00046-X PMID 21496613. Also see Singer HS. "Tourette's syndrome: from behaviour to biology". Lancet Neurol. 2005 Mar;4(3):149–59. doi:10.1016/S1474-4422(05)01012-4 PMID 15721825.
- Robertson MM. "Gilles de la Tourette syndrome: the complexities of phenotype and treatment". Br J Hosp Med (Lond). 2011 Feb;72(2):100–7. PMID 21378617
- Du JC, Chiu TF, Lee KM, et al. "Tourette syndrome in children: an updated review". Pediatr Neonatol. 2010 Oct;51(5):255–64. doi:10.1016/S1875-9572(10)60050-2 PMID 20951354
- Tourette Syndrome Association. Statement: Deep Brain Stimulation and Tourette Syndrome. Retrieved November 22, 2005.
- Malone DA Jr, Pandya MM. Behavioral neurosurgery. Adv Neurol. 2006;99:241–7. PMID 16536372
- 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
- Viswanathan A, Jimenez-Shahed J, Baizabal Carvallo JF, Jankovic J. Deep brain stimulation for Tourette syndrome: target selection. Stereotact Funct Neurosurg. 2012;90(4):213–24. PMID 22699684 doi: 10.1159/000337776
- Krauss JK (2002). "Deep brain stimulation for dystonia in adults. Overview and developments". Stereotactic and Functional Neurosurgery 78 (3–4): 168–182. doi:10.1159/000068963. PMID 12652041.
- Wu C, Sharan AD (2013 Jan-Feb). "Neurostimulation for the treatment of epilepsy: a review of current surgical interventions". Neuromodulation 16 (1): 10–24. PMID 22947069.
- Burn DJ, Tröster AI (September 2004). "Neuropsychiatric complications of medical and surgical therapies for Parkinson's disease". J Geriatr Psychiatry Neurol 17 (3): 172–80. doi:10.1177/0891988704267466. PMID 15312281.
- 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
- 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