Robert Zivadinov, Croatian neurologist and expert in magnetic resonance is only 39 years old, and has already made significant discoveries in the field of multiple sclerosis Robert Zivadinov, Croatian specialist for neurology and expert in magnetic resonance has for years now been numbered among the world's best researchers in the field of multiple sclerosis. The native of Rijeka who has spent the past four years researching this severe illness at the Jacobs Institute for Neurology in Buffalo in the US state of New York, is also one of the youngest physicians in the world holding the post of director of a top medical centre. Zivadinov has yet to reach the age of 40, and as far back as 2003 he was appointed head of the Jacobs Institute's Buffalo Centre for the Analysis of Magnetic Resonance. There he and his 24-member team of researchers, besides the illness itself, are studying the most advanced methods of magnetic resonance, techniques crucial to the discovery and monitoring of multiple sclerosis and many other neurological illnesses. At the same time he and his colleagues care for 4500 patients suffering from this illness, which is about the entire population of those who have fallen victim to multiple sclerosis in Croatia. The fact that in his almost 15-year career as a physician working abroad he has made pioneering discoveries about multiple sclerosis has resulting in the fact that Zivadinov currently spends upwards of 150 days a year travelling to congresses around the world to present some of the eighty expert research papers he has so far published in the world's pre-eminent medical journals. In October, he will be presenting 16 such works at the biggest global congress on multiple sclerosis in Prague where he has been invited as chief lecturer in the field of magnetic resonance and the re-myelination of the brain and spinal cord. There he will present new discoveries on the influence of the genetic type of multiple sclerosis on the seriousness of the disease as measured by various methods of magnetic resonance.

This international authority in the field of this serious disorder, from which 2 million people suffer world-wide, launched his career in 1993 in Trieste in Italy, where he, after graduating and doing his specialisation at the Faculty of Medicine in Rijeka, found employment at a clinic for neurology in Trieste and there founded a Centre for the Analysis of Magnetic Resonance. There he launched research the results of which made him a globally acclaimed researcher. He spoke to Nacional about this during his vacation at his parent's family home in Medveja near Opatija, where he has been staying since mid August with his wife Tina and their seven-month-old son Leon

"In Trieste I developed a technique for the quantification of magnetic resonance that makes it possible to measure atrophication of the brain, which is one of my greatest professional achievements. In 2001, my colleagues in Trieste and I published two very important papers in the medical journal Neurology and the Journal of Neurology, Neurosurgery & Psychiatry that are to this day my most cited papers. In the first paper, I established that if patients with multiple sclerosis are administered methyl-prednisone in cycles of three to six months there is a reduction of the atrophication of the brain. What is interesting is that some fifteen instances of clinical research were launched around the world based on that work, and pharmaceutical companies are to this day researching how effective a combination of that compound with existing medications is in treating multiple sclerosis. In the second work on cognitive disorders and brain atrophication, the first of its kind in the world, I established that in very young patients that have not been treated by any kind of therapy, brain atrophy developed over a two year period as a direct multiple sclerosis process. Up to then namely it was believed that only those patients who have the advanced phase of the disorder lose brain tissue."

As a result of the mentioned papers and seven years of successful research work at the Trieste clinic, Zivadinov had by 2000 become a respected expert in the field of brain atrophy research, especially as he was among the first in the world to introduce concrete procedures to measure the grey and white substances of that organ in clinical practice. It is likely as a result of that achievement that this Croatian physician was approached at the 2002 European Neurology Congress in Berlin by Frederick E. Munschauer, the director of Buffalo's Jacobs Institute for Neurology, who invited him to move there and become a professor of neurology at the Institute. As soon as he accepted, the Institute secured Zivadinov financing and gave him a year's time to round up a team of scientists in Buffalo and launch his research. When he started work in 2003, he was at the same time appointed the director of the Centre for Magnetic Resonance Analysis that operates in Buffalo as a part of the Jacobs Institute, at the University of Buffalo. He also became the executive director of a federation of the 17 largest centres for multiple sclerosis in the state of New York (the New York State Multiple Sclerosis Consortium). This institution has one of the world's largest databases on those suffering from multiple sclerosis, which have been systematically monitored over a ten-year period.
"At the Centre for Magnetic Resonance in Buffalo, I started with two people, while today my team numbers 24 experts in the fields of neurology, neuropsychology, physics, computer science and biostatistics.

What is interesting is that the people working in my team come from various parts of the world, so that my colleagues are Americans, Sudanese, Indians, Norwegians, Pakistanis, Czechs, Italians and so forth." Every year, three or four physicians or computer scientists from around the world do scholarship programs at the Centre headed by Robert Zivadinov, coming to Buffalo to specialise there for the research of multiple sclerosis and various methods of magnetic resonance. Along with that, the Centre hosts monthly seminars on magnetic resonance for hundreds of neurologists and radiologists from across the USA. The Centre for Magnetic Resonance was expanded in May with 1000 new square metres of floor space, equipped with the latest technology, an investment of 2.5 million dollars. Robert Zivadinov is currently engaged there in developing various kinds of software that should allow for the volumetric measurement of the atrophication of various parts of the brain and spinal cord in multiple sclerosis and in other neurological disorders. Work in that area brought him, he says, yet another key discovery, as he in the measurements of the volume of parts of the brain proved that the thalamus was the part of the brain hardest hit by multiple sclerosis. And while up to five years ago no one knew why the thalamus would be hit by this disorder at all, Zivadinov and his team proved that those suffering from advanced phases of multiple sclerosis have 15 percent less brain tissue, 20 to 25 percent less grey matter and as much as 50 percent less thalamus volume as a healthy person does. It should be said that the newest research papers published by Robert Zivadinov in this and the previous year have led to a significant change in the understanding of multiple sclerosis. "While in 2001 it was felt that the sickness was a predominantly de-myelination disorder of the white brain matter, characterised by the degeneration of the myelin which led to a weakening of the link between nerve cells in the brain, we have now proven something quite different. Our research and that of our colleagues around the world has shown that multiple sclerosis is a neurodegenerative disease that along with the white matter, also hits the grey matter, and as a result we can number it among disorders such as Alzheimer's, Parkinson's and similar afflictions. Knowledge in the field of multiple sclerosis has over recent years generally seen a tremendous change and progression. One of the most important achievements is that of German and American colleagues in 2005 when the so-called subpial cortical lesions were discovered, i.e. damage in the brain. They used pathological examination in which they coloured brain tissue with a base protein of myelin and discovered lesions that had not been visible up to then and are still not visible using magnetic resonance. This is certainly one of the most important achievements in the field of multiple sclerosis in the past two years because we learned for the first time that the disorder was not only where the lesions were, but also where they were not visible. And so it was discovered that in multiple sclerosis an enormous amount of lesions appear in the cortical, i.e. deep grey matter of the brain", said Zivadinov. He published a paper this year in the journal Neurology in which he revealed that besides lesions in the white substance and lesions between the white and grey matter of the brain, many smaller lesions appear in that organ in multiple sclerosis that are not visible in magnetic resonance (so-called inflammatory infiltrates). But, though not visible in that examination, they can, says Zivadinov, be indirectly proven by new methods of magnetic resonance such as magnetic transfer and spectroscopy, advanced techniques that are also used at the Centre in Buffalo. Zivadinov points out that intensive research is ongoing that would allow the invisible lesions in the grey brain matter to be visible to magnetic resonance in the near future.

THE FAMILY HOME of Robert Zivadinov at Orchard Park where he lives with his wife Tina and their seven month old son Leon“ "Modern medical technology has already improved existing magnetic resonance devices. After the standard 1.5 tesla power MRI devices, there are now already devices with a strength of three teslas. These devices, of which the one at our Centre in Buffalo is among the first in the USA, reveal significantly more lesions in the brain. This year it was, besides, proven that the most powerful existing device of 7 teslas, which only a few American institutes have, show even the tiniest lesions in grey matter. So no one can say anymore that a patient does not have lesions, but only that they probably cannot be seen."

Robert Zivadinov adds that clinical research is the most profitable area of work his Centre does. "We are a centre that reads the findings of magnetic resonances for multi-centre clinical research, which means that about 100 different centres around the world send us their magnetic resonance shots for our analysis. The analysis and research is done in collaboration with the world's largest pharmaceutical companies who provide massive funding for this kind of research, and that is one of the aspects of the financing of our centre. We currently cooperate with five pharmaceutical companies for whom we are working on five big clinical research programs." Zivadinov points out that pharmaceutical companies are in recent years exceptionally interested for research into mediations for multiple sclerosis. While there were in 2001, he says, only a few such companies, there are currently at least twenty that are launching research linked to multiple sclerosis. Zivadinov claims that the result of this interest is something that will in the future greatly advance the treatment of patients, these being oral medications. Up to now medications that have been administered by injections, such as interferones (Avonex, Rebif and Betaferon) or glatiramer acetate (Copaxone), have been crucial in the treatment of multiple sclerosis. Modern pharmaceutics, says Zivadinov, is now trying to get better results through the use of oral medications.

"In the past 15 years when it comes to medication for multiple sclerosis, the greatest achievement is the drug Natalizumab or Tysabri, which inhibits adhesive molecules on the periphery. Besides that, at least five new medications for multiple sclerosis will appear by 2010, and one of them is Fingolimod FTY720 – and oral drug that is a lysophospholipid agonist. We are also waiting for the drug laquinamod, which is a modified version of Linomid, a medication that has shown itself to be successful in reducing the number of attacks and lesions in the brain, while drug BG-12, i.e. a derivate of fumaric acid has shown similar results. Also awaited is a drug that inhibits B-lymphocytes and is called Rituximab, which could become the first effective medication for the primary-progressive form of multiple sclerosis. That drug has shown itself in research to be tremendously effective because there was as much as a 93 percent reduction of the development of lesions in the brain. Pharmaceutics has over recent years truly made steps forward when it comes to multiple sclerosis. While up to 2000, a brilliant result of drug therapy meant a reduction of 30 percent in attacks and 70 percent in lesions, the new drugs I have cited are significantly more effective. With them the number of attacks is reduced by as much as 60 to 70 percent, while the reduction in the development of new lesions in the brain is as much as 90 percent." Zivadinov claims that the money that pharmaceutical companies invest in the research into multiple sclerosis is almost equal to that spent on the research of all other neurological disorders put together. That this is the case is demonstrated by there currently being 150 large-scale clinical research programs into the sickness underway around the world. In addition to cooperation on clinical research, this medical centre is also financed by the state by way of the National Health Institute, which approves and pays for some research projects, five of which are currently being carried out in Buffalo. The rest of the money comes from private foundations such as the Foundation for Multiple Sclerosis, Parkinson's disease, and the research work at the centre is also financially assisted by some large global corporations.

At the Centre for Magnetic Resonance in Buffalo, I started with two people, while today my team numbers 24 experts in the fields of neurology, neuropsychology, physics, computer science and biostatistics "Financing is very important because you can be the best expert, but if you do not have money for research it is all in vain. There are no successful scientists in the world who are also not good businessmen. In order to be a real scientist in the USA, you have to have a nose for business. Without that there is nothing", says Zivadinov who confesses that this system of research work and of leading the Centre in fact suits him. He is very happy with his life in Buffalo, especially since he and his wife Tina fitted out their family home in Orchard Park not far from Buffalo. As far as his return to Croatia goes, he says that is not likely to happen soon. But he does point out that he would like cooperation with his colleagues in Croatia to be much more concrete. That is why he is inviting all young physicians and researchers to apply for scholarships awarded every year to four people by the Jacobs Institute in Buffalo in the amount of 13 to 26 thousand dollars.