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Deep brain stimulation for Parkinson's disease

A remarkable surgical procedure may relieve the symptoms of Parkinson’s disease (PD).The technique, which involves electrically stimulating specific parts of the brain, has recently been shown to help patients who do not respond to drug treatments, and may offer hope to PD patients worldwide. It is considered to be the most significant progress in the treatment of Parkinson’s disease since the discovery in the 1960s of levodopa – the most powerful drug known to alleviate PD symptoms.

Deep brain stimulation (DBS) has been familiar to neurologists and neurosurgeons since the 1960s as a way to locate and distinguish specific sites in the brain1. While studying this, they discovered that stimulation of certain brain structures suppresses the symptoms of neurological disorders such as Parkinson’s disease.

A stimulating idea

DBS is a variation of an old surgery, in which a small area of the brain – the thalamus or the globus pallidus – was destroyed, in order to treat tremor in multiple sclerosis or PD. DBS carries less risk because there is no destruction and the stimulation is adjustable and reversible. The technique involves inserting a wire into a particular part of the brain. It is then run under the patient’s skin to a small machine called an implantable pulse generator, which is placed under the skin on the chest. The generator sends small electrical currents through the wire to the brain.

DBS, however, was not used as a viable alternative to ablative therapies until the early 1990s2. Researchers at the MRC Cambridge Centre for Brain Repair in Cambridge investigated the part of the brain that causes PD – the subthalamic nucleus – which is stimulated by DBS3. Although this therapy worked for some PD patients, it was ineffective for the 40 per cent of patients who didn’t respond to drugs.

The breakthrough came through work by MRC-funded Professor Tipu Aziz, a neurosurgeon at Oxford University’s John Radcliffe Hospital, who identified another target in primate brains, the pedunculopontine nucleus4. When this target was stimulated, PD symptoms were alleviated, even in patients who were not responsive to drugs. The first DBS in this brain region in human patients was recently performed in Rome.

The DBS device, made by US medical technology company Medtronic Inc. was approved in Europe in 1995 for treating tremor in PD. Estimates are that the cost of DBS treatment will be recouped in just a few years. The therapy is now used worldwide – more than 30,000 people have received it – and is also being used to treat other disorders including dystonia, a much rarer disease than PD which affects children5. Professor Aziz’s team has also been testing DBS for the relief of chronic pain and to regulate blood pressure6. Currently, the MRC is carrying out a £1 million randomised clinical trial of DBS in different parts of the brain, and Medtronic is about to begin a trial of the technology for treating severe depression.

References

1. Meyers (1968). The surgery of the hyperkinetic disorders. In: Vinken & Bruyn. Handbook of clinical neurology. Amsterdam: North Holland, 844.

2. Benabid et al. (1991). Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. The Lancet, 337, 403.

3. Henderson & Dunnett (1998). Targeting the subthalamic nucleus in the treatment of Parkinson’s disease. Brain Res Bull, 46, 467.

4. Aziz et al. (1999). The role of the pedunculopontine region in basal-ganglia mechanisms of akinesa. Exp Brain Res, 129, 511.

5. Kupsch et al. (2003). The effects of frequency in pallidal deep brain stimulation for primary dystonia. J Neurology, 250, 1201.

6. Green et el. (2006). Stimulating the human midbrain to reveal the link between pain and blood pressure. Pain, 124, 349.

MRC, July 2006, updated January 2007

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