Clinical Neuroimmunology

The Clinical Neuroimmunology group under the direction of Prof. Dr. Friedemann Paul investigates inflammatory and autoimmune diseases of the nervous system such as multiple sclerosis (MS) and neuromyelitis optica (NMO). The team carries out numerous studies to improve diagnosis and treatment of multiple sclerosis and other diseases. The main focus is on developing so-called neuroprotective (nerve cell protecting) treatment approaches and establishing modern examination procedures such as MRI (magnetic resonance imaging), OCT (optical coherence tomography) and motion analysis.

Research focus
Multiple sclerosis

Multiple sclerosis (MS) is considered the most common chronic inflammatory disease of the central nervous system and primarily affects young adults. The disease is caused by autoimmune processes, meaning the body's immune system recognizes its own nervous system as "foreign" and causes an inflammatory reaction, resulting in damage to nerve cells and axons with their enveloping protective layer. Many different neurological symptoms, including paralysis, visual disturbances, abnormal sensations or balance problems, can occur.

The Clinical Neuroimmunology team focuses on developing and establishing new disease course and prognostic markers for MS. This includes, for example, improving possibilities in the field of magnetic resonance imaging (MRI) and ultra-high field MRI, or establishing new imaging techniques such as optical coherence tomography (OCT). The team is also interested in developing new tools for analysing movement disorders.

Because there is as yet no cure for MS, treatment strategies center primarily on improving symptoms and disease course. Accordingly, another area of the team’s activity is the development and conduct of clinical trials with the aim of improving treatment options in MS. This includes phase II to IV drug trials, which are carried out on our own or in collaboration with industry, and new non-drug treatment strategies, for example, in the treatment of depression and fatigue in MS.

 

Neuromyelitis optica
Neuromyelitis optica (NMO) has long been regarded as a variation of MS. Today we know that NMO is an independent disease, which is based on another disease mechanism.
Typical manifestations of NMO are, on the one hand, unilateral or bilateral optic neuritis, often leading to severe vision problems and, on the other hand, long-term inflammation in the spinal cord, which can lead to severe paralysis, abnormal sensations, gait disorders, and bladder dysfunction.
The disease is caused by an immune response to a cellular water channel known as aquaporin-4. Antibodies against this water channel can be detected in most patients with NMO. As with MS, there is currently no cure for NMO. Current therapeutic strategies focus on highly specific pharmacological interventions in the immune system.
The Clinical Neuroimmunology group is considered one of the leading centers in NMO research both nationally and internationally. New diagnostic approaches, e.g., with OCT or MRI imaging are tested and therapeutic studies conducted.
 
The group is a member of the neuromyelitis optica study group NEMOS and works closely with the US-based Guthy Jackson Charitable Foundation (GJCF). More information on neuromyelitis optica and the NEMOS study group can be found at: http://www.nemos-net.de. For more information on GJCF see: www.guthyjacksonfoundation.org.
 
Susac`s syndrome

Susac’s syndrome was first described in 1979. It is a rare and still poorly understood disorder of small blood vessels that mainly affects the brain, the retina of the eye, and the inner ear.

Typical symptoms include hearing and vision problems, as well as a variety of neurological problems such as memory and concentration disorders, behavioral changes, loss of balance, abnormal sensations, and paralysis, among others. The disease course can be quite diverse. It often comes to a stop after a few years, although for many patients a more or less significant disability remains. Treatment is primarily with immunosuppressive drugs.

The Clinical Neuroimmunology group is one of the few centers in Europe with a research focus on Susac’s syndrome. The main focuses of scientific interest are the mechanisms leading to Susac’s syndrome, diagnosis of the disease, and improvement of the therapeutic possibilities.

The group is a founding member of the European Susac Consortium (EUSAC). More information on Susac’s syndrome and EUSAC can be found at: http://www.eusac.net.

Imaging and image analysis
Significant developments in technology and data processing lead to rapid advances in the field of imaging of the central nervous system. Because of this, possibilities for the diagnosis and course assessment of MS and other neuroimmunological diseases are continuously improving and expanding. Alongside MRI imaging, which is constantly evolving, OCT imaging of the retina has established itself in MS research in recent years.
Thus, another focus of the group is MRI imaging and image analysis. Although MRI scans are now an integral part of MS diagnosis, the potential of this technology has not yet been fully exploited. Areas of activity of the Clinical Neuroimmunology group include the improvement of so-called conventional MRI techniques, the development of automated algorithms for image analysis and testing, and the establishment of new technologies such as ultra-high field MRI or other methods for detecting neurodegeneration.
A further focus alongside MRI imaging is OCT imaging. Since the retina evolutionarily belongs to the central nervous system, in many diseases of the central nervous system such as MS or NMO, characteristic changes in the retina structure occur which can be detected by OCT and observed in the disease course. An OCT examination is not burdensome for the patient, is doable within a few minutes, is especially suitable for the assessment of neurodegenerative processes, and provides an ideal complement to MRI imaging. In addition to applying the OCT technology, the Clinical Neuroimmunology team is involved in the standardized automated evaluation of OCT data according to established quality criteria, and provides a central evaluation service, e.g., in the context of studies. For more information about the OCT and the Berlin OCT Reading Center, see: http://www.neurodial.de
The Clinical Neuroimmunology group is also active in the field of automated, objective assessment of movement disorders, such as may occur in MS. By using commercially available motion capture devices in combination with appropriate evaluation algorithms, problems such as, for example, gait disturbances can be recorded in detail in MS patients, evaluated, and monitored over time.
Group leader
Prof. Dr. Friedemann Paul
Friedemann Paul has headed the Clinical Neuroimmunology group at the NeuroCure Clinical Research Center at the Charité since 2008. He studied medicine in Berlin and in 2003 specialised in neurology. Friedemann Paul has been a senior physician at the Charité since 2004, and directed the College Outpatient Clinic for Neuroimmunology at the Berlin Buch site since 2010. As group leader of Clinical Neuroimmunology, he works closely with basic scientists, neurologists and neuro-imaging researchers in conducting clinical studies to improve diagnosis of neuroimmunological diseases such as multiple sclerosis and neuromyelitis optica, and investigate new therapeutic strategies for these diseases.
Cooperation
  • Clinic for Neurology, Charité - Universitätsmedizin Berlin (Prof. Dr. M. Endres, Prof. Dr. L. Harms, Prof. Dr. H. Audebert, PD Dr. K. Ruprecht, PD Dr. H. Prüss, PD Dr. C. Finke)
  • Experimental and Clinical Research Center Berlin, Charité - Universitätsmedizin Berlin und Max Delbrück Center for Molecular Medicine (Prof. Dr. T. Niendorf, Dr. C. Infante)
  • Bernstein Center for Computational Neuroscience, Berlin (Prof. Dr. J. Haynes)
  • Clinic and Polyclinic for Neurology, University Hospital Muenster (PD Dr. Th. Duning, Dr. I. Kleffner, Prof. Dr. H. Wiendl))
  • Clinic and Polyclinic for Neurology, University Medical Center Hamburg-Eppendorf (Prof. Dr. C. Heesen)
  • Clinic for Neurology, Heinrich Heine University Düsseldorf (Prof. Dr. O. Aktas, PD Dr. P. Albrecht, Dr. M. Ringelstein, Prof. Dr. H.-P. Hartung)
  • Clinic for Neurology, Ruprecht-Karls University, Heidelberg (Dr. S. Jarius, Prof. Dr. B. Wildemann)
  • Clinic and Polyclinic for Neurology of the University of Ulm (Prof. Dr. H. Tumani, Prof. Dr. v. Arnim)
  • Department of Neurology with focus on neurovascular diseases, Hertie Institute for Clinical Brain Research, University Hospital of the Eberhard-Karls University Tübingen (Prof. U. Ziemann)
  • Clinic and Polyclinic for Neurology, University Hospital Carl Gustav Carus Dresden (PD Dr. T. Ziemssen)
  • Department of Neuropathology, University Medical Center Göttingen (Prof. Dr. W. Brück)
  • Clinic for Neurology, University Hospital Zurich (Dr. S. Schippling)
  • Beuth University of Applied Sciences Berlin (Prof. Dr. H. Dietze)
  • Neurology Department, Mayo Clinic, USA (Prof. B. Weinshenker)
  • Department of Neurosciences, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona Spain (Prof. Dr. P. Villoslada)
  • Department of Neurobiology, Weizman Institute of Science, Rehovot, Israel (Prof. Dr. A. Zangen)
  • Technion, Israel Institute of Technology, Haifa, Israel (Prof. Y. Moudim, Dr. S. Mandel)
  • Motognosis GmbH Berlin (A. Brandt)
  • Heidelberg Engineering GmbH, Heidelberg
  • Brainsway, Jerusalem, Israel
  • Hadassah Medical Center, Hebrew University, Jerusalem, Israel (Prof. T. Ben-Hur, Dr. N. Levin, Dr. N. Raz, Dr. S. Arzi)