Deep brain stimulation

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Deep brain stimulation
Intervention
Tiefe Hirnstimulation - Sonden RoeSchaedel ap.jpg
DBS-probes shown in X-ray of the skull (white areas around maxilla and mandible represent metal dentures and are unrelated to DBS devices)
MeSH D046690
MedlinePlus 007453

Deep brain stimulation (DBS) is a neurosurgical procedure involving the implantation of a medical device called a neurostimulator (sometimes referred to as a 'brain pacemaker'), which sends electrical impulses, through implanted electrodes, to specific parts of the brain (brain nucleus) for the treatment of movement and affective disorders. 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, chronic pain, major depression and obsessive–compulsive disorder (OCD).[1] Despite the long history of DBS,[2] its underlying principles and mechanisms are still not clear.[3][4] 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.[citation needed]

The Food and Drug Administration (FDA) approved DBS as a treatment for essential tremor in 1997,[citation needed] for Parkinson's disease in 2002,[5] dystonia in 2003,[6] and OCD in 2009.[7] 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 effective for some patients, potential for serious complications and side effects exists.

Components and placement[edit]

Reconstruction of DBS electrodes. Shown are the subthalamic nucleus (orange), red nucleus (green), the substantia nigra (yellow), the internal (cyan) and external pallidum (blue) and the striatum (red). Structural fibertracts traversing through this volume are visualized with color-coded fibers and cortical regions that they terminate in are visualized with translucent colors.[8]

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 or two different nuclei of the brain. The lead is connected to the IPG by the extension, an insulated wire that runs below the skin, 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.[9] The IPG can be calibrated by a neurologist, nurse, or trained technician to optimize symptom suppression and control side-effects.[10]

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 internus or the subthalamic nucleus; for OCD and Depression to the nucleus Accumbens; for incessant pain to the posterior thalamic region or periaqueductal gray; for Parkinson plus patients to two nuclei simultaneously, subthalamic nucleus and tegmental nucleus of pons, with the use of two pulse generators; and for epilepsy treatment to the anterion thalamic nucleus.[11]

All three components are surgically implanted inside the body. Lead implantation may take place under local anesthesia or with the patient under general anesthesia ("asleep DBS") such as for dystonia. A hole about 14 mm in diameter is drilled in the skull and the probe electrode is inserted stereotactically. During the awake procedure with local anesthesia, feedback from the patient is used to determine optimal placement of the permanent electrode. During the asleep procedure, intraoperative MRI guidance is used for direct visualization of brain tissue and device.[12] The installation of the IPG and extension leads occurs under general anesthesia.[13] The right side of the brain is stimulated to address symptoms on the left side of the body and vice versa.

Applications[edit]

Parkinson's disease[edit]

Insertion of electrode during surgery using a stereotactic frame

Parkinson's disease is a neurodegenerative disease whose primary symptoms are tremor, rigidity, bradykinesia, and postural instability.[14] DBS does not cure Parkinson's, but it can help manage some of its symptoms and subsequently improve the patient’s quality of life.[15] At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications, or whose medications have severe side-effects.[9] 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[16] and/or directly diminish the side-effects induced by Parkinsonian medications,[17] 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.[18]

DBS is approved in the United States by the Food and Drug Administration for the treatment of Parkinson's.[5] 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%).[19]

Chronic pain[edit]

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[20] 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.[21] DBS has also been applied for phantom limb pain.[22]

Major depression[edit]

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).[23] A number of neuroanatomical targets have been utilised for deep brain stimulation for TRD including the subgenual cingulate gyrus, nucleus accumbens,[24] ventral capsule/ventral striatum, inferior thalamic peduncle, and the lateral habenula.[23] A recently proposed target of DBS intervention in depression is the superolateral branch of the medial forebrain bundle (slMFB), its stimulation lead to surprisingly rapid antidepressant effects in very treatment resistant patients.[25]

The small patient numbers in the early trials of deep brain stimulation for TRD currently limit the selection of an optimal neuroanatomical target.[23] 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.[26] In fact, beneficial results have been documented in the neurosurgical literature, including a few instances in which deeply depressed patients were provided with portable stimulators for self-treatment.[27][28][29]

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.[30] The first randomized controlled study of DBS for the treatment of treatment resistant depression targeting the ventral capsule/ventral striatum area did not demonstrate a significant difference in response rates between the active and sham groups at the end of a 16-week study.[31]

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".[32]

Tourette syndrome[edit]

Further information: Treatment of Tourette syndrome

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.[33][34][35][36] 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".[37] As of 2006, there were five reports in patients with TS; all experienced reduction in tics and the disappearance of obsessive-compulsive behaviors.[37]

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.[38]

Robertson reports that DBS had been used on 55 adults as of 2011, remains an experimental treatment,[34] and "should only be conducted by experienced functional neurosurgeons operating in centres which also have a dedicated Tourette syndrome clinic".[34] 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."[37] Du et al (2010) say that "As an invasive therapy, DBS is currently only advisable for severely affected, treatment-refractory TS adults".[35] Singer (2011) says that "pending determination of patient selection criteria and the outcome of carefully controlled clinical trials, a cautious approach is recommended".[33] Viswanathan A et al (2012) say that DBS should be used in patients with "severe functional impairment that can not be managed medically".[39]

Other clinical applications[edit]

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.[40] The procedure has been tested for effectiveness in people with epilepsy that is resistant to medication.[41] DBS may control or eliminate epileptic seizures with programmed or responsive stimulation.

DBS of the septal areas of patients with schizophrenia have resulted in enhanced alertness, cooperation, and euphoria. Patients with narcolepsy and psychomotor seizures have also reportedly experienced euphoria and sexual thoughts with self-elicited DBS of the septal areas.[28]

Adverse effects[edit]

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.[42]

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.[citation needed]

As with all surgery there is the risk of infection and bleeding during and after a surgery. The foreign object placed may be rejected by the body or calcification of the implant might take place.[medical citation needed]

Mechanisms[edit]

The exact mechanism of action of DBS is not known.[43] There exist three hypotheses to explain the mechanisms of DBS:[44]

  1. Depolarization blockade: Electrical currents block the neuronal output at or near the electrode site.
  2. Synaptic inhibition: This causes an indirect regulation of the neuronal output by activating axon terminals with synaptic connections to neurons near the stimulating electrode.
  3. De-synchronization of abnormal oscillatory activity of neurons.

Deep brain stimulation represents an advance on previous treatments which involved pallidotomy (i.e., surgical ablation of the globus pallidus) or thalamotomy (i.e., surgical ablation of the thalamus).[45] Instead, a thin lead with multiple electrodes is implanted in the globus pallidus, nucleus ventralis intermedius thalami (Vim) or the subthalamic nucleus and electric pulses are used therapeutically. The lead from the implant is extended to the neurostimulator under the skin in the chest area.

See also[edit]

References[edit]

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  43. ^ Mogilner A.Y., Benabid A.L., Rezai A.R. (2004). "Chronic Therapeutic Brain Stimulation: History, Current Clinical Indications, and Future Prospects". In Markov, Marko; Paul J. Rosch. Bioelectromagnetic medicine. New York, N.Y: Marcel Dekker. pp. 133–51. ISBN 0-8247-4700-3. 
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Further reading[edit]

  • 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 (12): 1722–1728. doi:10.1002/mds.21551. PMID 17721929. 
  • Gildenberg Philip L (2005). "Evolution of neuromodulation". Stereotact Funct Neurosurg 83 (2–3): 71–79. doi:10.1159/000086865. PMID 16006778. 
  • Kringelbach ML, Jenkinson N, Owen SLF, Aziz TZ (2007). "Translational principles of deep brain stimulation". Nature Reviews Neuroscience 8 (8): 623–635. doi:10.1038/nrn2196. PMID 17637800. 
  • Schlaepfer TE, Bewernick BH, Kayser S, Hurlemann R, Coenen VA (2014). "Deep Brain Stimulation of the Human Reward System for Major Depression-Rationale, Outcomes and Outlook". Neuropsychopharmacology 39 (6): 1303–1314. doi:10.3109/15622975.2013.869619. PMID 24506290. 
  • Diamond A, Shahed J, Azher S, Dat-Vuong K, Jankovic J (May 2006). "Globus pallidus deep brain stimulation in dystonia". Mov. Disord. 21 (5): 692–5. doi:10.1002/mds.20767. PMID 16342255. 
  • Richter E.O., Lozano A.M. (2004). "Deep Brain Stimulation for Parkinson's Disease in Movement Disorders". In Markov, Marko; Paul J. Rosch. Bioelectromagnetic medicine. New York, N.Y: Marcel Dekker. pp. 265–76. ISBN 0-8247-4700-3. 

External links[edit]