Klinik und Poliklinik für Neurologie

Ataxias

The degenerative ataxias comprise a wide spectrum of hereditary and non-hereditary disorders with progressive ataxia as the prominent symptom. In most hereditary ataxias, the underlying gene mutations have been identified. Principally, it is distinguished between autosomal recessive ataxias - the most frequent of which is Friedreich´s ataxia (FRDA) - and the autosomal dominantly inherited ataxias which are also named spinocerebellar ataxias (SCA).The most frequent types of non-hereditary degenerative ataxias are the cerebellar variant of multiple system atrophy (MSA-C) and the sporadic adult-onset ataxias of unknown aetiology (SAOA). In the framework of large-scale national and international network projects we have designed and established an internet-based database of European SCA patients that contains entries of about 4000 European SCA patients and a standardized evaluation program that allows to study the natural history of SCA patients and to evaluate the effects of disease modifying drugs. Core of this evaluation program is a newly developed rating scale (Scale for the Assessment and Rating of Ataxia, SARA) that was shown to be a valid and reliable tool for the clinical evaluation of ataxia patients. We are coordinating an ongoing European natural history study of more than 500 patients with SCA1, SCA2, SCA3 and SCA6. Beyond that, we conduct a European multicenter observational study of individuals at risk for SCA1, SCA2, SCA3 and SCA6 (RISCA). RISCA aims to determine the incidence of disease manifestation in mutation carriers and to identify clinical signs that precede the onset of manifest ataxia. In addition, we are conducting SPORTAX, an observational study of patients with adult-onset sporadic ataxia. Soon, we will start the European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI), an international longitudinal cohort study of presymptomatic mutation carriers and symptomatic SCA3-patients that aims to develop innovative assessment instruments and disease markers, assess the impact of lifestyle factors on disease evolution and allows to develop a revised and improved model of this disease. This project may impact the diagnosis and routine management of SCA3-patients as well as the feasibility and design of interventional trials.

A particular focus of our research is neuroimaging using advanced MRI and PET methods. Our group is involved in interventional trials in degenerative ataxia. To foster therapeutic research in ataxia, the Ataxia Study Group (ASG) was founded.

Key Publications

Jacobi H, du Montcel ST, Bauer P, Giunti P, Cook A, Labrum R, Parkinson MH, Durr A, Brice A, Charles P, Marelli C, Mariotti C, Nanetti L, Panzeri M, Rakowicz M, Sulek A, Sobanska A, Schmitz-Hübsch T, Schöls L, Hengel H, Baliko L, Melegh B, Filla A, Antenora A, Infante J, Berciano J, van de Warrenburg BP, Timmann D, Szymanski S, Boesch S, Kang JS, Pandolfo M, Schulz JB, Molho S, Diallo A, Klockgether T. Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study. Lancet Neurol. 2015 Nov;14(11):1101-8. 

Reetz K, Dogan I, Costa AS, Dafotakis M, Fedosov K, Giunti P, Parkinson MH, Sweeney MG, Mariotti C, Panzeri M, Nanetti L, Arpa J, Sanz-Gallego I, Durr A, Charles P, Boesch S, Nachbauer W, Klopstock T, Karin I, Depondt C, vom Hagen JM, Schöls L, Giordano IA, Klockgether T, Bürk K, Pandolfo M, Schulz JB. Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis of baseline data. Lancet Neurol. 2015 Feb;14(2):174-82.

Klockgether T. Spinocerebellar ataxia type 2: progression before diagnosis. Lancet Neurol. 2014 May;13(5):445-6.

Jacobi H, Reetz K, du Montcel ST, Bauer P, Mariotti C, Nanetti L, Rakowicz M, Sulek A, Durr A, Charles P, Filla A, Antenora A, Schöls L, Schicks J, Infante J, Kang JS, Timmann D, Di Fabio R, Masciullo M, Baliko L, Melegh B, Boesch S, Bürk K, Peltz A, Schulz JB, Dufaure-Garé I, Klockgether T. Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data. Lancet Neurol 2013;12:650-8.

Jacobi H, Bauer P, Giunti P, Labrum R, Sweeney MG, Charles P, Dürr A, Marelli C, Globas C, Linnemann C, Schöls L, Rakowicz M, Rola R, Zdzienicka E, Schmitz-Hübsch T, Fancellu R, Mariotti C, Tomasello C, Baliko L, Melegh B, Filla A, Rinaldi C, van de Warrenburg BP, Verstappen CC, Szymanski S, Berciano J, Infante J, Timmann D, Boesch S, Hering S, Depondt C, Pandolfo M, Kang JS, Ratzka S, Schulz J, Tezenas du Montcel S, Klockgether T . The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology 2011;77:1035-41.

Klockgether T . Sporadic ataxia with adult onset: classification and diagnostic approach. Lancet Neurol 2010; 9:94-104.

Schmitz-Hübsch T, Coudert M, Bauer P, Giunti P, Globas C, Baliko L, Filla A, Mariotti C, Rakowicz M, Charles P, Ribai P, Szymanski S, Infante J, van de Warrenburg BP, Dürr A, Timmann D, Boesch S, Fancellu R, Rola R, Depondt C, Schöls L, Zdienicka E, Kang JS, Döhlinger S, Kremer B, Stephenson DA, Melegh B, Pandolfo M, di Donato S, du Montcel ST, Klockgether T. Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms. Neurology. 2008 Sep 23;71(13):982-9.

Schmitz-Hübsch T, Tezenas du Montcel S, Baliko L, Berciano J, Boesch S, Depondt C, Fancellu R, Giunti P, Globas C, Infante J, Kang J-S, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schöls L, Szymanski, MD, van de Warrenburg BP, Dürr A, Klockgether T . Scale for the Assessment and Rating of Ataxia: Development of a new clinical scale. Neurology 2006;66:1717-1720.


Prof. Dr. Thomas Klockgether
Prof. Dr. Thomas Klockgether

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