Deep brain stimulation (DBS)

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 remarkable therapeutic benefits for otherwise treatment-resistant movement and affective disorders such as chronic pain, Parkinson’s disease, tremor and dystonia. 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 is one of only a few neurosurgical methods that allows 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 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-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 neurosurgeon , 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 ventrointermedial 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 subthalamic nucleus.

All three components are surgically implanted inside the body. 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 thalamic slices from mice, that DBS causes nearby astrocytes 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 mimics ablation or "lesioning."

Applications

Parkinson's disease

Parkinson's disease (also known as paralysis agitans) 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.[5] 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.

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.

Using brain imaging, the researchers 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 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 environments. The changes reversed when the current was switched off.

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.

Another hypothetically interesting site for DBS in depression is the nucleus accumbens, as that region appears to be associated with pleasure and reward mechanisms. Experimental use of deep brain stimulation has shown promising results, with patients suffering from profound depression reporting relief from their symptoms.

 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 experimental procedure for the treatment of Tourette's, and more study is needed to determine whether long-term benefits outweigh the risk. 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". The  published reports of DBS in patients with TS showed  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." There may be serious short- and long-term risks associated with DBS in persons with head and neck tics.  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

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.

DBS has been used in the treatment of obsessive-compulsive disorder, phantom limb pain, and cluster headaches. Although the clinical efficacy is not questioned, the mechanisms by which DBS works is still debated. Long-term clinical observation has shown that the mechanism is not due to a progressive lesion, given that interruption of stimulation reverses its effects. 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 is being tested for effectiveness in patients with severe epilepsy.