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Deep Brain Stimulation
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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). 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, dystonia in 2003, and
OCD in 2009. 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
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
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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. 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 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.
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
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direct visualization of brain tissue and device. The installation of the IPG and
extension leads 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.
Applications
Parkinson's disease
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.
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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%).
Chronic pain
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.
Major depression
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. A recently proposed target of DBS intervention in depression
is the superolateral branch of the medial forebrain bundle (slMFB), its
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stimulation lead to surprisingly rapid antidepressant effects in very treatment
resistant patients.
The small patient numbers in the early trials of deep brain stimulation for TRD
currently limit the selection of an optimal 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. 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.
A systematic review of DBS for treatment-resistant depression and obsessive–
compulsive disorder identified 23 cases—nine for OCD, seven for treatmentresistant 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. 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.
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".
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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. 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
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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 people with epilepsy that is resistant to medication. 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.
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