nach oben

Neurotherapeutics

Erschienen in:

01.10.2014 | Review

Triadopathies: An Emerging Class of Skeletal Muscle Diseases

verfasst von: James J. Dowling, Michael W. Lawlor, Robert T. Dirksen

Erschienen in: Neurotherapeutics | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

Abstract

The triad is a skeletal muscle substructure responsible for the regulation of excitation–contraction coupling. It is formed by the close apposition of the T-tubule and the terminal sarcoplasmic reticulum. A rapidly growing list of skeletal myopathies, here referred to as triadopathies, are caused by gene mutations in components of the triad. These disorders, at their root, are caused by defects in excitation contraction coupling and intracellular calcium homeostasis. Secondary abnormalities in triad structure and/or function are also reported in several muscle diseases, most notably certain muscular dystrophies. This review highlights the current understanding of both primary and secondary triadopathies, and identifies important concepts yet to be fully addressed in the field. The emphasis of the review is both on the pathogenesis of triadopathies and their potential treatment.

Nur mit Berechtigung zugänglich

Engel A, Franzini-Armstrong C. Myology: basic and clinical. 3rd ed. McGraw-Hill, New York, 2004.

Melzer W, Herrmann-Frank A, Luttgau HC. The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibres. Biochim Biophys Acta 1995;1241:59-116.PubMed

Rossi AE, Dirksen RT. Sarcoplasmic reticulum: the dynamic calcium governor of muscle. Muscle Nerve 2006;33:715-731.PubMed

Nance JR, Dowling JJ, Gibbs EM, Bonnemann CG. Congenital myopathies: an update. Curr Neurol Neurosci Rep 2012;12:165-174.PubMed

Rosenberg H, Davis M, James D, Pollock N, Stowell K. Malignant hyperthermia. Orphanet J Rare Dis 2007;2:21.PubMedPubMedCentral

Rosenberg H, Sambuughin N, Riazi S, Dirksen R. Malignant hyperthermia susceptibility. In: Pagon RA, Adam MP, Bird TD, et al. (eds) GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2014; 2003 Dec 19 [updated 2013 Jan 31].

Denborough M. Malignant hyperthermia. Lancet 1998;352:1131-1136.PubMed

McCarthy EJ. Malignant hyperthermia: pathophysiology, clinical presentation, and treatment. AACN Clin Issues 2004;15:231-237.PubMed

Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB. Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006. Anesth Analg 2010;110:498-507.PubMed

10.

Donnelly AJ. Malignant hyperthermia. Epidemiology, pathophysiology, treatment. AORN J 1994;59:393-395.PubMed

11.

Gonsalves SG, Ng D, Johnston JJ, et al. Using exome data to identify malignant hyperthermia susceptibility mutations. Anesthesiology 2013;119:1043-1053.PubMed

12.

Stowell KM. DNA testing for malignant hyperthermia: the reality and the dream. Anesth Analg 2014;118:397-406.PubMed

13.

Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P. Mutations in RYR1 in malignant hyperthermia and central core disease. Hum Mutat 2006;27:977-989.PubMed

14.

Carpenter D, Ringrose C, Leo V, et al. The role of CACNA1S in predisposition to malignant hyperthermia. BMC Med Genet 2009;10:104.PubMedPubMedCentral

15.

Yarotskyy V, Dirksen RT. Cav1.1 in malignant hyperthermia. In: Weiss N, Koschak A (eds) Pathologies of calcium channels. Springer-Verlag, Berlin, 2014.

16.

Kim JH, Jarvik GP, Browning BL, et al. Exome sequencing reveals novel rare variants in the ryanodine receptor and calcium channel genes in malignant hyperthermia families. Anesthesiology 2013;119:1054-1065.PubMed

17.

Capacchione JF, Muldoon SM. The relationship between exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia. Anesth Analg 2009;109:1065-1069.PubMed

18.

Tobin JR, Jason DR, Challa VR, Nelson TE, Sambuughin N. Malignant hyperthermia and apparent heat stroke. JAMA 2001;286:168-169.PubMed

19.

Dlamini N, Voermans NC, Lillis S, et al. Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis. Neuromuscul Disord 2013;23:540-548.PubMed

20.

Jungbluth H, Dowling JJ, Ferreiro A, Muntoni F. 182nd ENMC International Workshop: RYR1-related myopathies, 15–17th April 2011, Naarden, The Netherlands. Neuromuscul Disord 2012;22:453-462.PubMed

21.

Jungbluth H. Central core disease. Orphanet J Rare Dis 2007;2:25.PubMedPubMedCentral

22.

Jungbluth H. Multi-minicore disease. Orphanet J Rare Dis 2007;2:31.PubMedPubMedCentral

23.

Wilmshurst JM, Lillis S, Zhou H, et al. RYR1 mutations are a common cause of congenital myopathies with central nuclei. Ann Neurol 2010;68:717-726.PubMed

24.

Clarke NF, Waddell LB, Cooper ST, et al. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. Hum Mutat 2010;31:E1544-E1550.PubMed

25.

Klein A, Lillis S, Munteanu I, et al. Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies. Hum Mutat 2012;33:981-988.PubMed

26.

Zhou H, Lillis S, Loy RE, et al. Multi-minicore disease and atypical periodic paralysis associated with novel mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Neuromuscul Disord 2010;20:166-173.PubMedPubMedCentral

27.

Illingworth MA, Main M, Pitt M, et al. RYR1-related congenital myopathy with fatigable weakness, responding to pyridostigimine. Neuromuscul Disord 2014;24:707-712.PubMed

28.

Dowling JJ, Lillis S, Amburgey K, et al. King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Neuromuscul Disord 2011;21:420-427.PubMed

29.

Jungbluth H, Lillis S, Zhou H, et al. Late-onset axial myopathy with cores due to a novel heterozygous dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. Neuromuscul Disord 2009;19:344-347.PubMed

30.

Amburgey K, Bailey A, Hwang JH, et al. Genotype-phenotype correlations in recessive RYR1-related myopathies. Orphanet J Rare Dis 2013;8:117.PubMedPubMedCentral

31.

Treves S, Jungbluth H, Muntoni F, Zorzato F. Congenital muscle disorders with cores: the ryanodine receptor calcium channel paradigm. Curr Opin Pharmacol 2008;8:319-326.PubMed

32.

Messina S, Hartley L, Main M, et al. Pilot trial of salbutamol in central core and multi-minicore diseases. Neuropediatrics 2004;35:262-266.PubMed

33.

Dowling JJ, Arbogast S, Hur J, et al. Oxidative stress and successful antioxidant treatment in models of RYR1-related myopathy. Brain 2012;135:1115-1127.PubMedPubMedCentral

34.

Andersson DC, Marks AR. Fixing ryanodine receptor Ca leak – a novel therapeutic strategy for contractile failure in heart and skeletal muscle. Drug Discov Today Dis Mechan 2010;7:e151-e157.

35.

Loy RE, Lueck JD, Mostajo-Radji MA, Carrell EM, Dirksen RT. Allele-specific gene silencing in two mouse models of autosomal dominant skeletal myopathy. PloS One 2012;7:e49757.PubMedPubMedCentral

36.

Amburgey K, McNamara N, Bennett LR, McCormick ME, Acsadi G, Dowling JJ. Prevalence of congenital myopathies in a representative pediatric united states population. Ann Neurol 2011;70:662-665.PubMed

37.

Maggi L, Scoto M, Cirak S, et al. Congenital myopathies–clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom. Neuromuscul Disord 2013;23:195-205.PubMed

38.

Takekura H, Nishi M, Noda T, Takeshima H, Franzini-Armstrong C. Abnormal junctions between surface membrane and sarcoplasmic reticulum in skeletal muscle with a mutation targeted to the ryanodine receptor. Proc Natl Acad Sci U S A 1995;92:3381-3385.PubMedPubMedCentral

39.

Hirata H, Watanabe T, Hatakeyama J, et al. Zebrafish relatively relaxed mutants have a ryanodine receptor defect, show slow swimming and provide a model of multi-minicore disease. Development 2007;134:2771-2781.PubMed

40.

Kushnir A, Betzenhauser MJ, Marks AR. Ryanodine receptor studies using genetically engineered mice. FEBS Lett 2010;584:1956-1965.PubMedPubMedCentral

41.

Jungbluth H, Wallgren-Pettersson C, Laporte J. Centronuclear (myotubular) myopathy. Orphanet J Rare Dis 2008;3:26.PubMedPubMedCentral

42.

Biancalana V, Beggs AH, Das S, et al. Clinical utility gene card for: Centronuclear and myotubular myopathies. Eur J Hum Genet 2012;20.

43.

Laporte J, Hu LJ, Kretz C, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet 1996;13:175-182.PubMed

44.

Das S, Dowling J, Pierson CR. X-linked centronuclear myopathy. In: Pagon RA, Adam MP, Ardinger HH, et al. (eds) GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2014. 2002 [updated 2011 Oct 6].

45.

Bitoun M, Maugenre S, Jeannet PY, et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet 2005;37:1207-1209.PubMed

46.

Bohm J, Biancalana V, Dechene ET, et al. Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy. Hum Mutat 2012;33:949-959.PubMedPubMedCentral

47.

Nicot AS, Toussaint A, Tosch V, et al. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet 2007;39:1134-1139.PubMed

48.

Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, et al. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology 2013;81:1205-1214.PubMedPubMedCentral

49.

Dowling JJ. Titin and centronuclear myopathy: The tip of the iceberg for TTN-ic mutations? Neurology 2013;81:1189-1190.PubMed

50.

Durieux AC, Prudhon B, Guicheney P, Bitoun M. Dynamin 2 and human diseases. J Mol Med 2010;88:339-350.PubMed

51.

Koutsopoulos OS, Kretz C, Weller CM, et al. Dynamin 2 homozygous mutation in humans with a lethal congenital syndrome. Eur J Hum Genet 2013;21:637-642.PubMedPubMedCentral

52.

Dowling JJ, Vreede AP, Low SE, et al. Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy. PLoS Genet 2009;5:e1000372.PubMedPubMedCentral

53.

Al-Qusairi L, Weiss N, Toussaint A, et al. T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase. Proc Natl Acad Sci U S A 2009;106:18763-18768.PubMedPubMedCentral

54.

Toussaint A, Cowling BS, Hnia K, et al. Defects in amphiphysin 2 (BIN1) and triads in several forms of centronuclear myopathies. Acta Neuropathol 2011;121:253-266.PubMed

55.

Durieux AC, Vignaud A, Prudhon B, et al. A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice. Hum Mol Genet 2010;19:4820-4836.PubMed

56.

Gibbs EM, Davidson AE, Telfer WR, Feldman EL, Dowling JJ. The myopathy-causing mutation DNM2-S619L leads to defective tubulation in vitro and in developing zebrafish. Dis Models Mechan 2014;7:157-161.

57.

Smith LL, Gupta VA, Beggs AH. Bridging integrator 1 (Bin1) deficiency in zebrafish results in centronuclear myopathy. Hum Mol Genet 2014;23:3566-3578.PubMed

58.

Lee E, Marcucci M, Daniell L, et al. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science 2002;297:1193-1196.PubMed

59.

Al-Qusairi L, Prokic I, Amoasii L, et al. Lack of myotubularin (MTM1) leads to muscle hypotrophy through unbalanced regulation of the autophagy and ubiquitin-proteasome pathways. FASEB J 2013;27:3384-3394.PubMed

60.

Fetalvero KM, Yu Y, Goetschkes M, et al. Defective autophagy and mTORC1 signaling in myotubularin null mice. Mol Cell Biol 2013;33:98-110.PubMedPubMedCentral

61.

Hnia K, Tronchere H, Tomczak KK, et al. Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle. J Clin Invest 2011;121:70-85.PubMedPubMedCentral

62.

Dowling JJ, Joubert R, Low SE, et al. Myotubular myopathy and the neuromuscular junction: a novel therapeutic approach from mouse models. Dis Models Mechan 2012;5:852-859.

63.

Robb SA, Sewry CA, Dowling JJ, et al. Impaired neuromuscular transmission and response to acetylcholinesterase inhibitors in centronuclear myopathies. Neuromuscul Disord 2011;21:379-386.PubMed

64.

Childers MK, Joubert R, Poulard K, et al. Gene therapy prolongs survival and restores function in murine and canine models of myotubular myopathy. Sci Transl Med 2014;6:220–10.

65.

Lawlor MW, Armstrong D, Viola MG, et al. Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy. Hum Mol Genet 2013;22:1525-1538.PubMedPubMedCentral

66.

Gibbs EM, Clarke NF, Rose K, et al. Neuromuscular junction abnormalities in DNM2-related centronuclear myopathy. J Mol Med 2013;91:727-737.PubMed

67.

Stamm DS, Aylsworth AS, Stajich JM, et al. Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia. Am J Med Genet A 2008;146A:1832-1841.PubMed

68.

Horstick EJ, Linsley JW, Dowling JJ, et al. Stac3 is a component of the excitation-contraction coupling machinery and mutated in Native American myopathy. Nat Commun 2013;4:1952.PubMedPubMedCentral

69.

Nelson BR, Wu F, Liu Y, et al. Skeletal muscle-specific T-tubule protein STAC3 mediates voltage-induced Ca2+ release and contractility. Proc Natl Acad Sci U S A 2013;110:11881-11886.PubMedPubMedCentral

70.

Jain D, Sharma MC, Sarkar C, et al. Tubular aggregate myopathy: a rare form of myopathy. J Clin Neurosci 2008;15:1222-1226.PubMed

71.

Misceo D, Holmgren A, Louch WE, et al. A dominant STIM1 mutation causes Stormorken syndrome. Hum Mutat 2014;35:556-564.PubMed

72.

Nesin V, Wiley G, Kousi M, et al. Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis. Proc Natl Acad Sci U S A 2014;111:4197-4202.PubMedPubMedCentral

73.

Bohm J, Chevessier F, Maues De Paula A, et al. Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am J Hum Genet 2013;92:271-278.PubMedPubMedCentral

74.

Feske S. ORAI1 and STIM1 deficiency in human and mice: roles of store-operated Ca2+ entry in the immune system and beyond. Immunol Rev 2009;231:189-209.PubMed

75.

Dirksen RT. Checking your SOCCs and feet: the molecular mechanisms of Ca2+ entry in skeletal muscle. J Physiol 2009;587:3139-3147.PubMedPubMedCentral

76.

Stathopulos PB, Schindl R, Fahrner M, et al. STIM1/Orai1 coiled-coil interplay in the regulation of store-operated calcium entry. Nat Commun 2013;4:2963.PubMedPubMedCentral

77.

Wei-Lapierre L, Carrell EM, Boncompagni S, Protasi F, Dirksen RT. Orai1-dependent calcium entry promotes skeletal muscle growth and limits fatigue. Nat Commun 2013;4:2805.PubMed

78.

Yarotskyy V, Protasi F, Dirksen RT. Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death. PloS One 2013;8:e77633.PubMedPubMedCentral

79.

Duke AM, Hopkins PM, Calaghan SC, Halsall JP, Steele DS. Store-operated Ca2+ entry in malignant hyperthermia-susceptible human skeletal muscle. J Biol Chem 2010;285:25645-25653.PubMedPubMedCentral

80.

Morgan-Hughes JA. Tubular aggregates in skeletal muscle: their functional significance and mechanisms of pathogenesis. Curr Opin Neurol 1998;11:439-442.PubMed

81.

Boncompagni S, Protasi F, Franzini-Armstrong C. Sequential stages in the age-dependent gradual formation and accumulation of tubular aggregates in fast twitch muscle fibers: SERCA and calsequestrin involvement. Age 2012;34:27-41.PubMedPubMedCentral

82.

Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 2012;11:891-905.PubMed

83.

Todd PK, Paulson HL. RNA-mediated neurodegeneration in repeat expansion disorders. Ann Neurol 2010;67:291-300.PubMedPubMedCentral

84.

Kimura T, Lueck JD, Harvey PJ, et al. Alternative splicing of RyR1 alters the efficacy of skeletal EC coupling. Cell Calcium 2009;45:264-274.PubMedPubMedCentral

85.

Kimura T, Nakamori M, Lueck JD, et al. Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2 + -ATPase in myotonic dystrophy type 1. Hum Mol Genet 2005;14:2189-2200.PubMed

86.

Tang ZZ, Yarotskyy V, Wei L, et al. Muscle weakness in myotonic dystrophy associated with misregulated splicing and altered gating of Ca(V)1.1 calcium channel. Hum Mol Genet 2012;21:1312-1324.PubMedPubMedCentral

87.

Fugier C, Klein AF, Hammer C, et al. Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy. Nat Med 2011;17:720-725.PubMed

88.

Morrison LA. Dystrophinopathies. Handb Clin Neurol 2011;101:11-39.PubMed

89.

Rahimov F, Kunkel LM. The cell biology of disease: cellular and molecular mechanisms underlying muscular dystrophy. J Cell Biol 2013;201:499-510.PubMedPubMedCentral

90.

Watkins SC, Hoffman EP, Slayter HS, Kunkel LM. Immunoelectron microscopic localization of dystrophin in myofibres. Nature 1988;333:863-866.PubMed

91.

Capote J, DiFranco M, Vergara JL. Excitation-contraction coupling alterations in mdx and utrophin/dystrophin double knockout mice: a comparative study. Am J Physiol Cell Physiol 2010;298:C1077-C1086.PubMedPubMedCentral

92.

Bellinger AM, Reiken S, Carlson C, et al. Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat Med 2009;15:325-330.PubMedPubMedCentral

93.

Fauconnier J, Thireau J, Reiken S, et al. Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy. Proc Natl Acad Sci U S A 2010;107:1559-1564.PubMedPubMedCentral

94.

Goonasekera SA, Lam CK, Millay DP, et al. Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle. J Clin Invest 2011;121:1044-1052.PubMedPubMedCentral

95.

Kirschner J, Lochmuller H. Sarcoglycanopathies. Handb Clin Neurol 2011;101:41-46.PubMed

96.

Andersson DC, Meli AC, Reiken S, et al. Leaky ryanodine receptors in beta-sarcoglycan deficient mice: a potential common defect in muscular dystrophy. Skelet Muscle 2012;2:9.PubMedPubMedCentral

97.

Amato AA, Brown RH, Jr. Dysferlinopathies. Handb Clin Neurol 2011;101:111-118.PubMed

98.

Kerr JP, Ward CW, Bloch RJ. Dysferlin at transverse tubules regulates Ca homeostasis in skeletal muscle. Front Physiol 2014;5:89.PubMedPubMedCentral

99.

Kerr JP, Ziman AP, Mueller AL, et al. Dysferlin stabilizes stress-induced Ca2+ signaling in the transverse tubule membrane. Proc Natl Acad Sci U S A 2013;110:20831-20836.PubMedPubMedCentral

100.

Gallardo E, Saenz A, Illa I. Limb-girdle muscular dystrophy 2A. Handb Clin Neurol 2011;101:97-110.PubMed

101.

Kramerova I, Kudryashova E, Wu B, Ottenheijm C, Granzier H, Spencer MJ. Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle. Hum Mol Genet 2008;17:3271-3280.PubMedPubMedCentral

102.

Castets P, Lescure A, Guicheney P, Allamand V. Selenoprotein N in skeletal muscle: from diseases to function. J Mol Med 2012;90:1095-1107.PubMed

103.

Arbogast S, Ferreiro A. Selenoproteins and protection against oxidative stress: selenoprotein N as a novel player at the crossroads of redox signaling and calcium homeostasis. Antioxid Redox Signal 2010;12:893-904.PubMed

104.

Rederstorff M, Castets P, Arbogast S, et al. Increased muscle stress-sensitivity induced by selenoprotein N inactivation in mouse: a mammalian model for SEPN1-related myopathy. PloS One 2011;6:e23094.PubMedPubMedCentral

105.

Castets P, Bertrand AT, Beuvin M, et al. Satellite cell loss and impaired muscle regeneration in selenoprotein N deficiency. Hum Mol Genet 2011;20:694-704.PubMed

106.

Jungbluth H, Sewry CA, Muntoni F. Core myopathies. Semin Pediatr Neurol 2011;18:239-249.PubMed

107.

Jurynec MJ, Xia R, Mackrill JJ, et al. Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle. Proc Natl Acad Sci U S A 2008;105:12485-12490.PubMedPubMedCentral

108.

Arbogast S, Beuvin M, Fraysse B, Zhou H, Muntoni F, Ferreiro A. Oxidative stress in SEPN1-related myopathy: from pathophysiology to treatment. Ann Neurol 2009;65:677-686.PubMed

109.

Castets P, Maugenre S, Gartioux C, et al. Selenoprotein N is dynamically expressed during mouse development and detected early in muscle precursors. BMC Develop Biol 2009;9:46.

110.

Majczenko K, Davidson AE, Camelo-Piragua S, et al. Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet 2012;91:365-371.PubMedPubMedCentral

111.

Klos Dehring DA, Vladar EK, Werner ME, Mitchell JW, Hwang P, Mitchell BJ. Deuterosome-mediated centriole biogenesis. Develop Cell 2013;27:103-112.

Titel: Triadopathies: An Emerging Class of Skeletal Muscle Diseases
verfasst von: James J. Dowling
Michael W. Lawlor
Robert T. Dirksen
Publikationsdatum: 01.10.2014
Verlag: Springer US
Erschienen in: Neurotherapeutics / Ausgabe 4/2014
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI: https://doi.org/10.1007/s13311-014-0300-3

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Was nützt die Kraniektomie bei schwerer tiefer Hirnblutung?

17.05.2024 Hirnblutung Nachrichten

Eine Studie zum Nutzen der druckentlastenden Kraniektomie nach schwerer tiefer supratentorieller Hirnblutung deutet einen Nutzen der Operation an. Für überlebende Patienten ist das dennoch nur eine bedingt gute Nachricht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2014

Heterogeneity of Leucine-Rich Repeat Kinase 2 Mutations: Genetics, Mechanisms and Therapeutic Implications

Repeat-Associated Non-AUG Translation and Its Impact in Neurodegenerative Disease

Epigenetic Mechanisms Underlying the Pathogenesis of Neurogenetic Diseases

Inherited Isolated Dystonia: Clinical Genetics and Gene Function

Epileptic Encephalopathies: New Genes and New Pathways