Asymptomatische HyperCKämie – Was nun?

Zusammenfassung

Immer wieder finden sich bei asymptomatischen Patienten erhöhte CK-Werte und der Verdacht auf eine Muskelerkrankung wird gestellt. Neuere Untersuchungen haben allerdings gezeigt, dass die CK-Referenzwerte für die verwendeten Testverfahren zu niedrig sind und neue höhere Grenzwerte wurden empfohlen. Bevor eine umfassende Abklärung in die Wege geleitet wird, sollten CK-Erhöhungen durch andere Ursachen, vor allem sportliche Aktivität und Medikamente wie Statine und Fibrate, ausgeschlossen werden. Findet sich keine Ursache für die CK-Erhöhung kann eine Muskelbiopsie durchgeführt werden. In ca. 25% der Fälle lässt sich mittels Biopsie, biochemischen und genetischen Untersuchungen eine definitive Diagnose stellen, wobei die Wahrscheinlichkeit einer Diagnosestellung umso höher ist, je höher die CK Werte und je jünger die Patienten sind. Eine genetische Abklärung ob ein Duchenne/Becker-Konduktorinnen-Status vorliegt erscheint bei Frauen mit CK-Erhöhung im gebärfähigen Alter sinnvoll. Die Prognose der asymptomatischen HyperCKämie ist insgesamt als sehr günstig anzusehen. Neue Empfehlungen eines EFNS Expertenpanels zur Diagnose und zur Abklärung einer asymptomatischen HyperCKämie werden diskutiert.

Abstract

In the presence of raised serum CK levels the suspicion of subclinical myopathy is frequently raised in asymptomatic patients. However, recent epidemiological studies indicate that the current CK reference values used might be too low and new reference values have been proposed. Before intensive investigations of patients with asymptomatic hyperCKemia are initiated, non-neuromuscular causes, e. g., exercise and drugs, should be excluded. A definitive diagnosis can be reached in approximately 25% of patients if muscle biopsies, biochemical and genetic studies are performed. Overall, the prognosis of asymptomatic hyperCKemia is benign and only a few patients develop a neuromuscular disorder. However, DNA analysis should be undertaken in young women with hyperCKemia because of the possibility of a Duchenne/Becker mutation carrier status. The recently published EFNS guidelines on the diagnostic approach to asymptomatic hyperCKemia are discussed.

Schlüsselwörter

Kreatinkinase - Myopathie - Referenzwert - Muskel - Biopsie

Key words

creatine kinase - myopathy - reference value - muscle - biopsy

• Literatur

• 1 Al-Jaberi MM, Katirji B. Serum Muscle Enzymes in Neuromuscular Disease. In: Katirji B, Kaminski HJ, Preston DC, Ruff RL, Shapiro BE. eds. Neuromuscular Disorders in Clinical Practice. Woburn, MA: Butterworth-Heinemann; 2002: 39-48
• 2 Bayer PM, Gabl F, Gergely Th et al. Isoenzymes of creatine kinase in the perinatal period (author’s transl). J Clin Chem Clin Biochem 1977; 15: 349-352
• 3 Brancaccio P, Maffulli N, Limongelli FM. Creatine kinase monitoring in sport medicine. British Medical Bulletin 2007; 81-82: 209-230
• 4 Brewster LM, Mairuhu G, Sturk A et al. Distribution of creatine kinase in the general population: implications for statin therapy. Am Heart J 2007; 154: 655-661
• 5 Nardin RA, Zarrin AR, Horowitz GL et al. Effect of newly proposed CK reference limits on neuromuscular diagnosis. Muscle Nerve 2009; 39: 494-497
• 6 Noakes TD. Effect of exercise on serum enzyme activities in humans. Sports Med 1987; 4: 245-267
• 7 Mougios V. Reference intervals for serum creatine kinase in athletes. British journal of sports medicine 2007; 41: 674-678
• 8 Lazarim FL, Antunes-Neto JMF, da Silva FOC et al. The upper values of plasma creatine kinase of professional soccer players during the Brazilian National Championship. J Sci Med Sport 2009; 12: 85-90
• 9 Finsterer J, Mittendorfer B, Neuhuber W et al. Influence of disposable, concentric needle electrodes on muscle enzyme and lactate serum levels. J Electromyogr Kinesiol 2002; 12: 329-337
• 10 Kyriakides T, Angelini C, Schaefer J et al. EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCKemia. European journal of neurology: the official journal of the European Federation of Neurological Societies 2010;
• 11 Lilleng H, Abeler K, Johnsen SH et al. Variation of serum creatine kinase (CK) levels and prevalence of persistent hyperCKemia in a Norwegian normal population. The Tromsø Study. Neuromuscul Disord. 2011
• 12 Harper CR, Jacobson TA. The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr Opin Lipidol 2007; 18: 401-408
• 13 Kuncl RW.. Agents and mechanisms of toxic myopathy. Current Opinion in Neurology 2009; 22: 506-515
• 14 Bruckert E, Hayem G, Dejager S et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients – the PRIMO study. Cardiovasc Drugs Ther 2005; 19: 403-414
• 15 Berardo A, Dimauro S, Hirano M. A diagnostic algorithm for metabolic myopathies. Curr Neurol Neurosci Rep 2010; 10: 118-126
• 16 Fernandez C, de Paula AM, Figarella-Branger D et al. Diagnostic evaluation of clinically normal subjects with chronic hyperCKemia. Neurology 2006; 66: 1585-1587
• 17 Dabby R, Sadeh M, Herman O et al. Asymptomatic or minimally symptomatic hyperCKemia: histopathologic correlates. Isr Med Assoc J 2006; 8: 110-113
• 18 Filosto M, Tonin P, Vattemi G et al. The role of muscle biopsy in investigating isolated muscle pain. Neurology 2007; 68: 181-186
• 19 Joy JL, Oh SJ. Asymptomatic hyper-CK-emia: an electrophysiologic and histopathologic study. Muscle & nerve 1989; 12: 206-209
• 20 Malandrini A, Orrico A, Gaudiano C et al. Muscle biopsy and in vitro contracture test in subjects with idiopathic HyperCKemia. Anesthesiology 2008; 109: 625-628
• 21 Prelle A, Tancredi L, Sciacco M et al. Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels. Journal of neurology 2002; 249: 305-311
• 22 Reijneveld JC, Notermans NC, Linssen WH et al. Benign prognosis in idiopathic hyper-CK-emia. Muscle Nerve 2000; 23: 575-579
• 23 Simmons Z, Peterlin BL, Boyer PJ et al. Muscle biopsy in the evaluation of patients with modestly elevated creatine kinase levels. Muscle Nerve 2003; 27: 242-244
• 24 Podnar S. Comparison of parametric and nonparametric reference data in motor unit potential analysis. Muscle Nerve 2008; 38: 1412-1419
• 25 D’Adda E, Sciacco M, Fruguglietti ME et al. Follow-up of a large population of asymptomatic/oligosymptomatic hyperckemic subjects. J Neurol 2006; 253: 1399-1403
• 26 Capasso M, De Angelis MV, Di Muzio A et al. Familial idiopathic hyper-CK-emia: an underrecognized condition. Muscle Nerve 2006; 33: 760-765
• 27 Ruffert H, Wehner M, Deutrich C et al. Malignant hyperthermia. The ugly. Anaesthesist 2007; 56: 923-929
• 28 Capacchione JF, Muldoon SM. The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia. Anesth Analg 2009; 109: 1065-1069
• 29 Figarella-Branger D, Kozak-Ribbens G, Rodet L et al. Pathological findings in 165 patients explored for malignant hyperthermia susceptibility. Neuromuscul Disord 1993; 3: 553-556
• 30 Wappler F, Fiege M, Steinfath M et al. Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis. Anesthesiology 2001; 94: 95-100
• 31 Girard T, Treves S, Voronkov E et al. Molecular genetic testing for malignant hyperthermia susceptibility. Anesthesiology 2004; 100: 1076-1080
• 32 Urwyler A, Deufel T, McCarthy T et al. Guidelines for molecular genetic detection of susceptibility to malignant hyperthermia. Br J Anaesth 2001; 86: 283-287
• 33 Tachi N, Wakai S, Yutoh Y et al. Asymptomatic hyperCKemia: detection of an isolated carrier of Duchenne muscular dystrophy. J Child Neurol 1990; 5: 351-353
• 34 Hoogerwaard EM, Ginjaar IB, Bakker E et al. Dystrophin analysis in carriers of Duchenne and Becker muscular dystrophy. Neurology 2005; 65: 1984-1986
• 35 Carbone I, Bruno C, Sotgia F et al. Mutation in the CAV3 gene causes partial caveolin-3 deficiency and hyperCKemia. Neurology 2000; 54: 1373-1376
• 36 Hanisch F, Müller CR, Grimm D et al. Frequency of calpain-3 c.550delA mutation in limb girdle muscular dystrophy type 2 and isolated hyperCKemia in German patients. Clin Neuropathol 2007; 26: 157-163
• 37 Nguyen K, Bassez G, Krahn M et al. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Arch Neurol 2007; 64: 1176-1182
• 38 Prelle A, Rigoletto C, Moggio M et al. Asymptomatic familial hyperCKemia associated with desmin accumulation in skeletal muscle. Journal of the Neurological Sciences 1996; 140: 132-136
• 39 Hanisch F, Grimm D, Zierz S et al. Frequency of the FKRP mutation c.826C>A in isolated hyperCKemia and in limb girdle muscular dystrophy type 2 in German patients. J Neurol 2010; 257: 300-301
• 40 Angelini C, Fanin M, Menegazzo E et al. Homozygous alpha-sarcoglycan mutation in two siblings: one asymptomatic and one steroid-responsive mild limb-girdle muscular dystrophy patient. Muscle & nerve 1998; 21: 769-775
• 41 Zouvelou V, Manta P, Kalfakis N et al. Asymptomatic elevation of serum creatine kinase leading to the diagnosis of 4q35 facioscapulohumeral muscular dystrophy. J Clin Neurosci 2009; 16: 1218-1219
• 42 Merlini L, Sabatelli P, Columbaro M et al. Hyper-CK-emia as the sole manifestation of myotonic dystrophy type 2. Muscle & nerve 2005; 31: 764-767
• 43 Teijeira S, San Millán B, Fernández JM et al. Myoadenylate deaminase deficiency: clinico-pathological and molecular study of a series of 27 Spanish cases. Clin Neuropathol 2009; 28: 136-142