Klinik und Poliklinik für Neurologie

Neuromuscular disorders

Neuromuscular disorders comprise a wide spectrum of hereditary and non-hereditary diseases with muscle weakness, exercise intolerance, myalgia and skeletal muscle wasting as characteristic symptoms. The Department of Neurology, University Hospital of Bonn, runs a highly spezialized neuromuscular diagnostic and research laboratory as well as a neuromuscular outpatient clinic. This Neuromuscular Center Bonn is certified by the Deutsche Gesellschaft für Muskelkranke e.V. (DGM) and constitutes a sub-center both of the Bonn Center for Orphan Disease Research and Therapy (Zentrum für Seltene Erkrankungen Bonn, ZSEB, zseb.uni-bonn.de) and of the neuromuscular center of North Rhine-Westphalia, Germany (Muskelzentrum Nordrhein).

Our major research interests are neuromuscular diseases with multisystemic manifestations affecting the central nervous system as well as metabolic myopathies. We have a special clinical and research focus on mitochondrial disorders and myotonic dystrophies. We further focus on the pathophysiology of muscle disorders, in particular the interaction of the various mechanisms (structural and metabolic deficits, inflammation and regeneration, neurogenic and myopathic reactions, etc.) and attempt to differentiate these elements and their order.

In mitochondrial diseases, we examine clinical, biochemical, molecular genetic and myopathological characteristics of various mitochondrial syndromes. Our studies include analyses of segregation patterns and metabolic effects of primary mitochondrial DNA mutations, analyses of recombination processes of mitochondrial DNA molecules in human skeletal muscle tissue, and analyses of the secondary effects of nuclear DNA mutations on mitochondrial DNA maintenance in various mitochondrial, further neuromuscular and neurological disorders like protein aggregation myopathies and motor neuron diseases. Our current projects further deal with analyses of mitochondrial function and DNA integrity in neurodegenerative diseases and epilepsy. Recently, we described and functionally characterized Mitochondrial Genome Maintenance Exonuclease 1 (MGME1), the first identified mitochondrial exonuclease directly involved in mitochondrial DNA replication. MGME1 loss-of-function mutations are a clinically relevant cause of specific multisystemic mitochondrial diseases. Currently, we particularly focus on mitochondrial DNA maintenance disorders, i.e. mitochondrial multiple deletions/rearrangements and depletion syndromes. Further, we examine clinical and neuroimaging features of brain involvement in patients with mitochondrial encephalomyopathies. The Neuromuscular Center Bonn is a clinical partner and patient recruiting center of mitoNET and is part of a web-based registry for patients with proven or suspected mitochondrial disorders (mitoREGISTER), funded by the German Federal Ministry of Education and Research (www.mitonet.org). In cooperation with spezialized clinicians, we implemented clinical practice guidelines for the diagnosis and treatment of mitochondrial disorders in Germany, Switzerland and Austria, edited by the German Neurological Society (DGN).

In myotonic dystrophy type 1 (DM1, Curschmann-Steinert disease) and myotonic dystrophy type 2 (DM2, proximal myotonic myopathy PROMM), we are especially interested in brain involvement. We are running longitudinal clinical and brain MRI studies on morphological and functional brain involvement in DM1 and DM2 patient cohorts and are member of an international working group on brain involvement in DM.

Our group is further involved in cardiac MRI and whole-body high-field neuromuscular MRI studies in order to characterize specific patterns of skeletal muscle involvement in various hereditary and metabolic myopathies.

The Neuromuscular Center Bonn is a treatment center for patients with Pompe disease and participates in clinical investigator-initiated phenotyping and treatment studies (i.e. longterm-effects of enzyme replacement therapy with alglucosidase alfa).

Key Publications

Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, Dimauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Nat Genet. 2013 Feb; 45(2): 214-219.

Mokbel N, Ilkovski B, Kreissl M, Memo M, Jeffries CM, Marttila M, Lehtokari VL, Lemola E, Grönholm M, Yang N, Menard D, Marcorelles P, Echaniz-Laguna A, Reimann J, Vainzof M, Monnier N, Ravenscroft G, McNamara E, Nowak KJ, Laing NG, Wallgren-Pettersson C, Trewhella J, Marston S, Ottenheijm C, North KN, Clarke NF. K7del is a common TPM2 gene mutation associated with nemaline myopathy and raised myofibre calcium sensitivity. Brain. 2013 Jan 31. [Epub ahead of print]

Vielhaber S, Debska-Vielhaber G, Peeva V, Kudin AP, Schöler S, Minin I, Schreiber S, Dengler R, Kollewe K, Zuschratter W, Kornblum C, Zsurka G, Kunz WS. Mitofusin 2 mutations affect mitochondrial function by mitochondrial DNA depletion. Acta Neuropathol. 2013 Feb; 125(2): 245-256.

Tschampa HJ, Urbach H, Greschus S, Kunz WS, Kornblum C. Neuroimaging characteristics in mitochondrial encephalopathies associated with the m.3243A>G MTTL1 mutation. J Neurol 2012 Nov 30. [Epub ahead of print]

Regnery C, Kornblum C, Hanisch F, Vielhaber S, Strigl-Pill N, Grunert B, Müller-Felber W, Glocker FX, Spranger M, Deschauer M, Mengel E, Schoser B. 36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy. Journal of Inherited Metabolic Disease 2012, 35(5): 837-845.

Minnerop M, Weber B, Schoene-Bake JC, Roeske S, Mirbach S, Ansbach C, Schneider-Gold C, Betz RC, Helmstaedter C, Tittgemeyer M, Klockgether T, Kornblum C. The brain in Myotonic Dystrophy 1 and 2: evidence for a predominant white matter disease. Brain 2011; 134(Pt 12): 3527-3543.

Reimann J, Kornblum C, Tolksdorf K, Brück W, van Landeghem FK. Myopathy and neuropathy with pipestem capillaries and vascular activated complement deposition. Neurology 2011; 77(4): 401-403.

Fratter C, Gorman G, Stewart JD, Buddles M, Smith C, Evans J, Seller A, Poulton J, Roberts M, Hanna MG, Rahman S, Omer SE, Klopstock T, Schoser B, Kornblum C, Czermin B, Lecky B, Blakely EL, Craig K, Chinnery P, Turnbull DM, Horvath R, Taylor RW. The clinical, histochemical and molecular spectrum of PEO1 (Twinkle)-linked adPEO. Neurology 2010; 18; 74(20): 1619-1626.

Zsurka G, Hampel KG, Nelson I, Jardel D, Mirandola S, Sassen R, Kornblum C, Marcorelles P, Lavoue S, Lombes A, Kunz WS. Severe epilepsy as the major symptom of new mutations in the mitochondrial tRNAPhe gene. Neurology 2010; 9; 74(6): 507-512.

Reimann J, Jacobson L, Vincent A, Kornblum C. Endplate destruction due to maternal antibodies in arthrogryposis multiplex congenita. Neurology 2009, 73(21): 1806-1808.

Minnerop M, Lüders E, Specht K, Ruhlmann J, Schneider-Gold C, Schröder R, Thompson P.M., Toga A.W., Klockgether T, Kornblum C. Grey and white matter loss along cerebral midline structures in myotonic dystrophy type 2. J Neurol 2008; 255(12): 1904-1909.

Zsurka G, Kraytsberg Y, Kudina T, Kornblum C, Elger CE, Khrapko K, Kunz WS. Recombination of mitochondrial DNA in skeletal muscle of individuals with multiple mitochondrial DNA heteroplasmy. Nat Genet. 2005; 37(8): 873-877.

Dr. Jens Reimann
Dr. Jens Reimann
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