A small electrode implanted in the most primitive areas of the brain can help those disabled by Parkinson’s disease lead an independent life. Can it do the same for those crippled by psychiatric disorders? /// JENNIFER STASTNY investigates

Margaret Maker was in her early fifties when her body started slipping out of her control. At a time when she should have been settling into a healthy late-middle age, she felt unco-ordinated, stiff and slow. Eighteen months later, at the age of 55, she was diagnosed with Parkinson’s disease. The average age of onset is 60.

Although she was prescribed levodopa (L-dopa) – the standard treatment for Parkinson’s, which shores up flagging levels of dopamine in the brain – the degenerative disease soon left her unable to trust her physical abilities. She stopped cooking for fear of dropping a hot dish on her feet. Her hobby of fine needlepoint transformed into an ordeal highlighting her diminished fine motor co-ordination. Limbs that were stubbornly rigid when she willed them to move would tremble involuntarily when she wished they would be still. “It got to the stage where I would wonder how I was going to walk from one side of the room to the other,” she says.

When her Johannesburg-based neurologist recommended deep brain stimulation, a process that involves implanting a tiny electric probe deep into the brain, Maker felt she had nothing left to lose. If DBS could give her back her body, she was willing to give it a try.

A DBS system consists of a probe about 1,5 mm wide with four small electrodes at the bottom, a battery-operated pacemaker, and a thin connecting wire. The probe is inserted about 6 cm deep in the brain at a very specific target area, where it emits a low-voltage, high-frequency electric pulse drawn from the pacemaker via a connecting wire that runs under the skin. The pacemaker itself is also implanted under the skin, in the pectoral (chest) area.

Why exactly an electric pulse at a target area in the brain helps alleviate the symptoms of Parkinson’s disease is anyone’s guess. “No one knows,” says Dr Roger Melvill, the Cape Town neurosurgeon who operated on Maker. “All we know is that the electrical stimulus interrupts neurological pathways in the brain, and that certain neural pathways are affected in movement disorders such as Parkinson’s and essential tremor.”

Melvill, a pioneer of deep-brain surgery in South Africa, trained in Sweden to bring the technology to the country in the early Nineties. Back then, deep-brain surgery meant doing a pallidotomy, in which an electric probe was used to heat and destroy a small group of dysfunctional brain cells at the target site. Today’s deep brain stimulation is less damaging and completely reversible: if the pacemaker is off, the probe is silent and brain functioning will eventually return to normal – which, in the case of Parkinson’s sufferers, means the return of unwanted, debilitating symptoms.

Measure twice, cut once
Implanting a deep-brain stimulator is a simple procedure, but one that must be executed with great precision and care. Before cutting, the neurosurgeon needs to know exactly where the probe needs to go. The first step in the process is an MRI scan, which maps the exact location of the target structure in three dimensions. Because her tremor was so severe, Maker had to be put under general anaesthetic for her MRI, which requires that she remain dead still to obtain a clear picture.

Once the MRI was done, the x, y and z co-ordinates it produced were used to position a stereotactic device consisting of a metal “halo” screwed into Maker’s skull and a movable arc that ran perpendicular to it. Once in position, the centre point of the halo and arc pointed to the globus pallidus, deep within Maker’s brain. The globus pallidus is one of three possible targets for the treatment of Parkinson’s.

Surgery could now go ahead. Maker’s head was shaved and she was given a local anaesthetic. A C-shaped incision was made in her head and the scalp flapped open to reveal the skull, through which a small burrhole was drilled so that the probe could be advanced – a process Melvill reassured her would feel much like going to the dentist. Maker was conscious throughout so that the surgeon could ensure that the electrode was correctly placed and not interfering with normal brain functioning.

Maker recalls how reassuring Melvill’s team was throughout the procedure – even when things went a little awry. “There was a nurse sitting next to me whose only job was to hold my hand and make sure that I was comfortable. Dr Melvill kept talking to me, telling me what they were doing and asking questions, such as what day of the week it was, where did I live, and so on,” she says. “At one point I knew something had gone wrong because he stopped talking. I asked what was happening. He said some air might have gotten into my bloodstream, and I was to blow hard into the mask.”

According to Melvill, the anaesthetist had grown concerned that a small amount of air might have entered a nicked vein in Maker’s head. If an air bubble made it to her heart, it could cause an “air lock” and the heart might stop pumping. By blowing hard into the mask, Maker increased the pressure in her chest and lowered the chance of an air bubble being sucked into the heart. “We took a preventive measure that avoided what could have been a serious problem,” says Melvill.

Air embolism, neural damage, stroke, psychosis – all of these are risks associated with implanting a DBS system. But once the surgery is over, the electrode is in position and the optimal setting is found for the pacemaker (which may take a little trial and error), the risks are minimal. And, as far as Maker is concerned, well worth it: “I had been out of the hospital for seven days when my husband turned to me and said, ‘I can’t believe the difference’. Then he started crying, so I started crying. Last February, I went overseas to visit my children. Before the implant, travelling alone would have been worrying for both me and my husband.”

Maker does not hesitate to recommend deep brain stimulation for anyone who is a good medical candidate for it – as long as they can afford it. Such specialised medical technology does not come cheap. According to Jaco van der Walt, managing director of Creatori Health, the local distributor for deep brain stimulators, a single-probe DBS system can cost R52 000. In cases where a movement disorder affects both the left and the right side of the body, a probe may need to be inserted in both sides of the brain, pushing up the cost to R83 000 – and that’s excluding specialists’ fees and hospital costs.

Not all medical aid funds are willing to cover the cost. “A few medical aids see DBS as a quality-of-life thing, and clearly their patients’ quality of life is not a priority,” says Van der Walt. Even if a medical aid fund does pay for the initial implant, it sometimes get sticky about paying to replace the battery, which lasts anywhere from three to seven years and costs upwards of R30 000 to replace. “Reimbursement is not just a problem for battery replacements, but also for the implantation of the system,” says Van der Walt.

The case for psychosurgery
In South Africa, DBS is currently used only for the treatment of movement disorders such as Parkinson’s and essential tremor, but there is a chance that it will be applied to psychiatric ailments such as obsessive-compulsive disorder (OCD) and Tourette’s syndrome within the next decade. Research is currently under way on 12 patients being treated for obsessive-compulsive disorder in the Netherlands – with some encouraging and surprising results.

“We are busy with the double-blind phase of the research, which means the patients have had the DBS electrodes inserted and calibrated, and we are in the process of randomly switching the pacemaker on for two weeks and off for two weeks in a way that neither the doctor nor the patient knows whether the unit is on or off,” says Dr Damiaan Denys, chair of psychiatry at the Academic Medical Centre in Amsterdam and lead researcher on the study.

“We were going to have the pacemaker on for three months and off for three months, but found that the difference was so remarkable that it was quite obvious – and difficult for the patient – when the pacemaker was off. So we decided to reduce the period to two weeks.” The official results of the research – the largest project of its kind in the world – are due for release in early 2008.

Back in South Africa, Melvill is understandably coy about the possibility of deep brain stimulation for psychiatric conditions. “When people hear psychosurgery, they think about what was done to people in concentration camps in Nazi Germany. They worry that it may be used as a way to control people, or to ‘decriminalise’ criminals,” he says.

Because of this shady history, Denys’s study had to pass a rigorous review by the Academic Medical Centre’s ethics committee. There are two main questions around the ethics of psychiatric surgery, he says: what kind of procedures do you allow, and who are your subjects?

“Procedures should be limited to ‘medical’ conditions and not used on, for example, criminals or rich people who are too lazy to take a pill,” he says. “And in treating medical conditions, you need to choose conditions that have very clear targets in the brain, such as obsessive-compulsive disorder or depression. Something like schizophrenia does not have a clear target in the brain, so is unsuitable for DBS.”

To DBS or not to DBS?
To meet ethical guidelines, each of the patients who took part in Denys’s OCD study had to meet three strict criteria. First, they had to be among the 10 per cent of OCD patients who do not respond to drug or cognitive behavioural therapies. Second, their obsessive behaviour had to be disabling; for example, compelling them to wash their hands virtually non-stop for 10 or 12 hours a day. Finally, a successful treatment would allow them to lead a full life.

In other words, they should not also be drug addicts, or nearing 100 years of age, or hotel heiresses with a drinking problem. Except for the OCD, their lives were pretty much in order.

Despite their efforts to meet (and exceed) ethical expectations, Denys and his team encountered some entirely unexpected dilemmas in the course of the study. One young woman discovered that, even though the implant did nothing to reduce her OCD symptoms, it did make her happy – happier than she had ever been in her life.

It came as no surprise when she asked the researchers to leave the pacemaker settings as they were.

“After much debate, we decided that, as doctors, we are interested in reducing symptoms,” says Denys. “We are not in the business of making people happy.” Much to her dismay, the settings on her pacemaker were adjusted until they had a positive effect on her OCD.

In another case, deep brain stimulation managed to rein in a 55- year-old patient’s OCD – along with his compulsive thirst for knowledge, a trait his wife of 30 years had grown to love in him. Although he finally recognised in himself the person his father used to be, and far preferred his calmer, more introverted self, his wife was less than pleased. “She was struggling to live with this new person and was even considering divorce,” says Denys. “Eventually we managed to convince them to go to marriage counselling.”

For Denys, these experiences shattered a belief still held by much of his profession: that psychiatric conditions can be treated by tinkering with the brain. “Before the study, I was convinced I could achieve a lot with drugs, and that psychotherapy, while interesting, was not necessary. When I started working with DBS, I thought, ‘Finally, here is a way to intervene with the brain in a pure, uncomplicated way’.

“What I discovered was that you need to go to a lot of psychological effort to help these people cope with their new lives. It was a paradoxical message for me: that fixing the brain also needs one to heal the mind.”

Regardless of whether DBS remains a treatment for movement disorders or whether it gains wider acceptance as a treatment for psychiatric disorders, it remains a technology that could be open to abuse by the unscrupulous. In a world where Viagra is taken for recreational purposes, it is not inconceivable that a brain implant that makes you feel sexually alive again – as DBS did for many of Denys’s male patients – might be abused. “DBS is a very promising therapy for OCD, but it should always be an end-of-line therapy, used only when other possibilities have been exhausted, and only in an academic hospital with ethical pursuits,” says Denys.

But medical technology remains the proverbial Pandora’s Box of the modern world: once the lid on a new treatment is open, it rarely stays in the ethically monitored academic domain. The best we can do is to set clear guidelines for responsible use and hope that patients and practitioners alike go to the effort of following them.

They are, after all, in everyone’s best interests. “Brain implantation can make us question our humanity in a very fundamental way,” says Denys. “It can change who we are. It should not be done lightly.”