Von Neuropathie bis ZNS: Systemische Amyloidose früh erkennen und behandeln

Der Fokus dieses Übersichtsartikels (CME) liegt auf der Erkennung typischer Symptome einschließlich neuromuskulärer, systemischer und seltener ZNS-Manifestationen, den Erfordernissen und Fallstricken hinsichtlich der diagnostischen Verfahren, den typischen Befunden in der Elektromyografie (EMG), Elektroneurografie (NLG) und weiteren elektrophysiologischen Funktionstests sowie den aktuellen Therapieoptionen.

Abstract

Systemic amyloidosis is an important differential diagnosis in progressive polyneuropathies. ATTRv-amyloidosis (hereditary) typically affects peripheral nerves and/or the heart, while ATTRwt-amyloidosis predominantly presents as cardiomyopathy but can also cause neurological symptoms. AL amyloidosis often progresses rapidly and is painful. Early diagnosis and a holistic, interdisciplinary approach to patients is crucial given the therapeutic options now available.

Schlüsselwörter

systemische Amyloidose - neuromuskuläre Manifestation - ATTR-Amyloidose - AL-Amyloidose - Therapie

Key words

systemic amyloidosis - neuromuscular manifestation - therapie

Publikationsverlauf

Artikel online veröffentlicht:
01. Dezember 2025

• Literatur

• 1 Pinto MV, Dyck PJB, Liewluck T. Neuromuscular amyloidosis: Unmasking the master of disguise. Muscle Nerve 2021; 64: 23-36
• 2 Coelho T, Marques W, Dasgupta NR. et al. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA 2023; 330: 1448-1458
• 3 Fontana M, Berk JL, Gillmore JD. et al. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. N Engl J Med 2025; 392: 33-44
• 4 Karam C, Mauermann ML, Gonzalez-Duarte A. et al. Diagnosis and treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States: Recommendations from a panel of experts. Muscle Nerve 2024; 69: 273-287
• 5 Buxbaum JN, Eisenberg DS, Fandrich M. et al. Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee. Amyloid 2024; 31: 249-256
• 6 Grogan M, Scott CG, Kyle RA. et al. Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System. J Am Coll Cardiol 2016; 68: 1014-1020
• 7 Merlini G, Dispenzieri A, Sanchorawala V. et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers 2018; 4: 38
• 8 Adams D, Ando Y, Beirao JM. et al. Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy. J Neurol 2021; 268: 2109-2122
• 9 Conceicao I, Gonzalez-Duarte A, Obici L. et al. "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst 2016; 21: 5-9
• 10 Coutinho P, da Silva A, de Lima J. et al. Forty years of experience with type 1 amyloid neuropathy: review of 483 cases. In. In: Glenner GG, e Costa PP, de Freitas AF, eds Amyloid and Amyloidosis. Amsterdam: Excerpta Medica; 1980: 88-98
• 11 Adams D, Suhr OB, Hund E. et al. First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy. Curr Opin Neurol 2016; 29: S14-S26
• 12 Coelho T, Ines M, Conceicao I. et al. Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy. Neurology 2018; 91: e1999-e2009
• 13 Adams D. Recent advances in the treatment of familial amyloid polyneuropathy. Ther Adv Neurol Disord 2013; 6: 129-139
• 14 Pernice HF, Knorz AL, Wetzel PJ. et al. Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis. Scientific Reports 2024; 14: 10111
• 15 Gentile L, Coelho T, Dispenzieri A. et al. A 15-year consolidated overview of data in over 6000 patients from the Transthyretin Amyloidosis Outcomes Survey (THAOS). Orphanet J Rare Dis 2023; 18: 350
• 16 Papagianni A, Ihne S, Zeller D. et al. Clinical and apparative investigation of large and small nerve fiber impairment in mixed cohort of ATTR-amyloidosis: impact on patient management and new insights in wild-type. Amyloid 2022; 29: 14-22
• 17 Russell A, Hahn C, Chhibber S. et al. Utility of Neuropathy Screening for Wild-Type Transthyretin Amyloidosis Patients. Can J Neurol Sci 2021; 48: 607-615
• 18 Kokotis P, Manios E, Schmelz M. et al. Involvement of small nerve fibres and autonomic nervous system in AL amyloidosis: comprehensive characteristics and clinical implications. Amyloid 2020; 27: 103-110
• 19 Rajkumar SV, Gertz MA, Kyle RA. Prognosis of patients with primary systemic amyloidosis who present with dominant neuropathy. Am J Med 1998; 104: 232-237
• 20 Muchtar E, Derudas D, Mauermann M. et al. Systemic Immunoglobulin Light Chain Amyloidosis-Associated Myopathy: Presentation, Diagnostic Pitfalls, and Outcome. Mayo Clin Proc 2016; 91: 1354-1361
• 21 Soontrapa P, Jones FJS, Milone M. et al. Clinicopathologic Features, Pathogenesis, and Treatment of Monoclonal Gammopathy-Associated Myopathies. Neurology 2025; Oct 7 105 (07) e214101
• 22 Sommer C, Birklein F, Hund E. Systemische ATTR-Amyloidosen – Hereditäre Amyloidneuropathien und andere Organmanifestationen 3. Auflage. Aufl. Bremen: UNI-MED; 2024
• 23 Liao R, Jain M, Teller P. et al. Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation 2001; 104: 1594-1597
• 24 Ney S, Ihle P, Ruhnke T. et al. Epidemiology of cardiac amyloidosis in Germany: a retrospective analysis from 2009 to 2018. Clin Res Cardiol 2023; 112: 401-408
• 25 Taipa R, Sousa L, Pinto M. et al. Neuropathology of central nervous system involvement in TTR amyloidosis. Acta Neuropathol 2023; 145: 113-126
• 26 Namiranian D, Geisler S. Neuromuscular Complications of Systemic Amyloidosis. Am J Med 2022; 135: S13-S19
• 27 Muchtar E, Derudas D, Mauermann M. et al. Systemic Immunoglobulin Light Chain Amyloidosis-Associated Myopathy: Presentation, Diagnostic Pitfalls, and Outcome. Mayo Clin Proc 2016; 91: 1354-1361
• 28 Sueyoshi T, Ueda M, Jono H. et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol 2011; 42: 1259-1264
• 29 Al Yaseen M, Al Zahid H, Al-Haroon S. Amyloid Deposits in the Ligamentum Flavum Related to Lumbar Spinal Canal Stenosis and Lumbar Disc Degeneration. Cureus 2022; 14: e26221
• 30 Hahn K, Urban P, Meliß RR. et al. Karpaltunnelsyndrom und ATTR-Amyloidose. Handchir Mikrochir Plast Chir 2018; 50: 329-334
• 31 Yanagisawa A, Ueda M, Sueyoshi T. et al. Knee osteoarthritis associated with different kinds of amyloid deposits and the impact of aging on type of amyloid. Amyloid 2016; 23: 26-32
• 32 Damy T, Adams D, Bridoux F. et al. Amyloidosis from the patient perspective: the French daily impact of amyloidosis study. Amyloid 2022; 29: 165-174
• 33 Adams D, Koike H, Slama M. et al. Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nature Reviews Neurology 2019; 15: 387-404
• 34 Ticau S, Sridharan GV, Tsour S. et al. Neurofilament Light Chain as a Biomarker of Hereditary Transthyretin-Mediated Amyloidosis. Neurology 2021; 96: e412-e422
• 35 Sachau J, Appel C, Reimer M. et al. Test-retest reliability of a simple bedside-quantitative sensory testing battery for chronic neuropathic pain. Pain Rep 2023; 8: e1049
• 36 Rolke R, Baron R, Maier C. et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006; 123: 231-243
• 37 Sletten DM, Suarez GA, Low PA. et al. COMPASS 31: a refined and abbreviated Composite Autonomic Symptom Score. Mayo Clin Proc 2012; 87: 1196-1201
• 38 Kollmer J, Weiler M, Purrucker J. et al. MR neurography biomarkers to characterize peripheral neuropathy in AL amyloidosis. Neurology 2018; 91: e625-e634
• 39 Arvidsson S, Eriksson R, Anan I. et al. Enlarged cross-sectional area in peripheral nerves in Swedish patients with hereditary V30M transthyretin amyloidosis. Ann Med 2023; 55: 2239269
• 40 Nathani D, Spies J, Barnett MH. et al. Nerve biopsy: Current indications and decision tools. Muscle Nerve 2021; 64: 125-139
• 41 Freeman R, Gonzalez-Duarte A, Barroso F. et al. Cutaneous amyloid is a biomarker in early ATTRv neuropathy and progresses across disease stages. Ann Clin Transl Neurol 2022; 9: 1370-1383
• 42 Leonardi L, Adam C, Beaudonnet G. et al. Skin amyloid deposits and nerve fiber loss as markers of neuropathy onset and progression in hereditary transthyretin amyloidosis. Eur J Neurol 2022; 29: 1477-1487
• 43 Adams D, Slama M. Hereditary transthyretin amyloidosis: current treatment. Curr Opin Neurol 2020; 33: 553-561
• 44 Carvalho A, Rocha A, Lobato L. Liver transplantation in transthyretin amyloidosis: issues and challenges. Liver Transpl 2015; 21: 282-292
• 45 Merlini G, Plante-Bordeneuve V, Judge DP. et al. Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. J Cardiovasc Transl Res 2013; 6: 1011-1020
• 46 Gillmore JD, Judge DP, Cappelli F. et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med 2024; 390: 132-142
• 47 Judge DP, Alexander KM, Cappelli F. et al. Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy. J Am Coll Cardiol 2025; 85: 1003-1014
• 48 Adams D, Polydefkis M, Gonzalez-Duarte A. et al. Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study. Lancet Neurol 2021; 20: 49-59
• 49 Adams D, Tournev IL, Taylor MS. et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid 2023; 30: 1-9
• 50 Karlstedt E, Jimenez-Zepeda V, Howlett JG. et al. Clinical Experience With the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis. J Card Fail 2019; 25: 147-153
• 51 Michalon A, Renaud L, Machacek M. et al. Prediction of Cardiac ATTR Depletion by NI006 (ALXN2220) Using Mechanistic PK/PD Modeling. Clin Pharmacol Ther 2025; 117: 261-269
• 52 Muchtar E, Dispenzieri A, Buadi FK. et al From CyBorD to Dara-CyBorD: ASCT Utilization Trends in AL Amyloidosis, A 15-Year Analysis. Blood Adv 2025; doi:10.1182/bloodadvances.2025016586
• 53 Obici L, Callaghan R, Ablett J. et al. Consensus recommendations on holistic care in hereditary ATTR amyloidosis: an international Delphi survey of patient advocates and multidisciplinary healthcare professionals. BMJ Open 2023; 13: e073130