In Context

www.thelancet.com/neurology Vol 13 March 2014 243

“I would say I’ve seen two miracles in my clinical experience”, says Paul Krack, head of the Movement Disorder Unit in the Department of Psychiatry and Neurology at University Hospital Grenoble, France. The fi rst was in Paris, in 1993. As a trainee neurologist he attended a meeting of the “Club des Mouvements Anormaux”, where he witnessed a video presentation of the fi rst patient to undergo bilateral subthalamic nucleus (STN) stimulation in Grenoble. Off treatment, the patient was rigid due to Parkinson’s disease. But as the switch that controlled the tiny electrode inserted into the patient’s brain was fl icked on, a seemingly magical transformation took place before the astonished onlookers. “He started getting up, smiling, moving, and that was so impressive”, recalls Krack. “All the people present stood up and applauded; it was a very important moment that I will never forget”.

Years later, having devoted much of his career to under-standing the eff ects of STN stimulation on behaviour, Krack saw his second miracle: a patient extremely disabled with what was once seen as a completely non-organic affl iction, obsessive compulsive disorder, became free of symptoms after the same type of procedure he had witnessed in Paris. Now, Krack says, the world is poised for a revolution in psychiatry over the coming decades, with psychosurgery increasingly used as an interventional tool. “Today deep brain stimulation [DBS] is totally experimental in psychiatry, but eventually it will become a treatment”, he contends. “I’m working on behaviour in patients with neurological problems and patients with psychiatric problems, and for me there are no borders between the two”.

Borders have never been a problem for Krack. When you're born in a country as small as Luxembourg, he says, “you're obliged to learn languages, and that opens up the world”. Although he didn't have to go too far afi eld for his early training in medicine, opting to cross the border into Germany and the University of Giessen. But it wasn't plain sailing at fi rst. Krack had diffi culty applying himself to his studies until he came into contact with his fi rst patient with Parkinson's disease, during a short sabbatical in Birmingham, UK. “That's when I fell in love with neurology”, he recalls, and his passion grew during his training in general neurology back in Giessen. It was during this time that he fi rst encountered Günther Deuschl, an expert on movement disorders at the University of Freiburg; after striking up a friendship, Krack would often consult with Deuschl about his most diffi cult cases. When Deuschl became a professor at the University of Kiel just as Krack's general training came to an end in 1995, the young man was thrilled to be invited to be part of a new department specialising in movement disorders and DBS.

Having witnessed the eff ects of DBS during that early trip to Paris, Krack was keen to learn more about the technique, and there was one person in particular he was keen to learn from. The patient had been presented by Pierre Pollak, a specialist in experimental treatments for Parkinson's disease at the University of Grenoble. One phone call from Deuschl later, and Krack, along with his wife and young son, was packing his bags for a year in France that would prove pivotal in his career. “That was the best year of my life”, he says. “I could dedicate myself to a couple of patients who I could follow for the full year. Grenoble was absolutely the best place to learn what Parkinson's disease is, and there were so many opportunities to do clinical research”. After returning to Kiel in 1996, Krack helped to build the department into Germany's leading centre for DBS, before a job off er from Pollak tempted him back to Grenoble, where he's been since 2001.

Fascinated by the behavioural aspects of Parkinson's disease in particular, Krack studied the role of the basal ganglia and the eff ects of STN stimulation on emotions. He developed the concept of hyperdopaminergic and hypodo-paminergic behaviour, “which is nowadays the concept that is almost unanimously accepted and helps to guide the clinical management of patients with Parkinson’s disease”, Deuschl notes. At one end of the behavioural spectrum there is hypodopaminergic behaviour, characterised by a lack of motivation. At the other extreme are the behavioural addictions that stem from a surfeit of motivation. “We are confronted by a continuum of opposite motivational states”, says Krack. “Behaviour determines the quality of life more than the motor aspects of Parkinson’s disease” he adds, “and as these dopamine-dependent aspects of behaviour can be infl uenced, it has become very obvious to me that neurologists must understand the psychology of Parkinson’s disease in order to improve patient management”.

In the coming years, Krack is determined to play his part in bringing DBS and psychosurgery out of the shadows. “Surgery that changes personality in ‘non-organic’ disease —even if the patient is explicitly asking for it—is confronted by hurdles, not only because of the abuse of psychosurgery in the past, but also because of oppositions between the world of non-biological psychiatry on the one hand and neuroscience on the other hand”, he explains. Trying to reconcile these opposing schools of thought is not a task for the faint hearted, but Krack is more than equal to the job according to Deuschl: “The motor of his actions is not making a career”, he says of his former student, “but solving scientifi c questions”.

David Holmes

Profi lePaul Krack: deeper brain stimulation

See Review page 287