title: The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey.
abstract: Recent advances in understanding amyotrophic lateral sclerosis (ALS) have delivered new questions. Disappointingly, the initial enthusiasm for transgenic mouse models of the disease has not been followed by rapid advances in therapy or prevention. Monogenic models may have inadvertently masked the true complexity of the human disease. ALS has evolved into a multisystem disorder, involving a final common pathway accessible via multiple upstream aetiological tributaries. Nonetheless, there is a common clinical core to ALS, as clear today as it was to Charcot and others. We stress the continuing relevance of clinical observations amid the increasing molecular complexity of ALS.
authors: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors: Martin R
authors: MR
authors: Turner
authors: Queen Mary University of London, London, UK University of Lisbon, Lisbon, Portugal.
authors: Michael
authors: M
authors: Swash
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology*; D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009626:Terminology as Topic
keywords: CLINICAL NEUROLOGY; GENETICS; MOLECULAR BIOLOGY; MOTOR NEURON DISEASE; PRION
references: Neurology. 2013 Apr 23;80(17):1590-7
references: 23553481
references: J Med Genet. 2012 Apr;49(4):258-63
references: 22499346
references: Nat Rev Neurol. 2011 Nov;7(11):603-15
references: 21989245
references: Neurology. 2012 Oct 16;79(16):1732-9
references: 23071166
references: Acta Neurol Scand. 1985 Jun;71(6):480-4
references: 4024859
references: Science. 2012 Jun 22;336(6088):1511-3
references: 22723400
references: Ann Neurol. 2007 May;61(5):427-34
references: 17469116
references: BMJ. 2004 Feb 28;328(7438):514-7
references: 14988196
references: Science. 2014 Sep 5;345(6201):1139-45
references: 25081482
references: J Neurol. 2010 Oct;257(10):1713-7
references: 20532545
references: Muscle Nerve. 1992 Feb;15(2):226-8
references: 1549145
references: J Neurol Neurosurg Psychiatry. 2013 Jan;84(1):116-7
references: 23033352
references: Neurology. 1957 Feb;7(2):124-34
references: 13400219
references: Neurology. 2009 Sep 8;73(10):805-11
references: 19738176
references: Trends Neurosci. 2014 May;37(5):247-55
references: 24690272
references: Neuron. 2012 Mar 22;73(6):1216-27
references: 22445348
references: Lancet Neurol. 2011 Mar;10(3):253-63
references: 21349440
references: J Neurol Neurosurg Psychiatry. 2011 Aug;82(8):853-4
references: 20562391
references: Science. 2006 Oct 6;314(5796):130-3
references: 17023659
references: Ann Neurol. 2013 Jul;74(1):20-38
references: 23686809
references: Exp Neurol. 2014 Dec;262 Pt B:91-101
references: 24780888
references: Acta Neuropathol. 2014 Mar;127(3):451-8
references: 24445903
references: Lancet Neurol. 2012 Apr;11(4):323-30
references: 22406228
references: J Neurol Neurosurg Psychiatry. 2012 Apr;83(4):399-403
references: 22100761
references: Brain. 2008 Jun;131(Pt 6):1540-50
references: 18469020
references: J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1232-8
references: 24648037
references: J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):740-6
references: 21402743
references: Cortex. 2012 Jul;48(7):936-44
references: 21924711
references: Brain. 1997 Oct;120 ( Pt 10):1723-37
references: 9365366
references: J Anat. 2014 Jan;224(1):45-51
references: 24010870
references: Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):487-93
references: 23879681
references: Neurology. 2003 Apr 22;60(8):1252-8
references: 12707426
references: BMJ. 2014;348:g3387
references: 24879816
references: Science. 2014 Sep 5;345(6201):1118-9
references: 25190778
references: J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):102-8
references: 21836033
references: JAMA Neurol. 2014 Sep;71(9):1102-10
references: 25023276
references: Brain. 1986 Oct;109 ( Pt 5):939-52
references: 3779374
references: Brain. 2005 Mar;128(Pt 3):472-6
references: 15634730
references: Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3548-53
references: 21321227
references: J Neurol Neurosurg Psychiatry. 1988 Feb;51(2):165-8
references: 3346681
references: Neurology. 2006 Jan 24;66(2):265-7
references: 16434671
references: Neurology. 2005 Jan 11;64(1):32-7
references: 15642900
references: Amyotroph Lateral Scler. 2012 May;13(3):245-50
references: 22424125
references: J Neurol Neurosurg Psychiatry. 1970 Jun;33(3):338-57
references: 5431724
references: Muscle Nerve. 2014 Apr;49(4):469-77
references: 24273101
references: J Neurol Neurosurg Psychiatry. 2011 Aug;82(8):843-9
references: 21515558
references: Amyotroph Lateral Scler Frontotemporal Degener. 2013 Sep;14(5-6):479-80
references: 23509957
references: Lancet Neurol. 2012 Mar;11(3):232-40
references: 22305801
references: Ann Neurol. 1987 Nov;22(5):580-6
references: 3501273
references: Amyotroph Lateral Scler. 2011 Jul;12(4):283-9
references: 21702735
references: Brain. 2012 Sep;135(Pt 9):2883-91
references: 22661746
references: Hum Hered. 2011;71(4):281-8
references: 21846995
references: Neurology. 2002 Sep 10;59(5):773-5
references: 12221178
references: Science. 2014 Sep 5;345(6201):1192-4
references: 25103406
references: J Neurol. 1994 Jun;241(7):448-55
references: 7931447
references: Amyotroph Lateral Scler Frontotemporal Degener. 2013 May;14 Suppl 1:19-32
references: 23678877
references: J Neurol Neurosurg Psychiatry. 1998 Dec;65(6):950-1
references: 9854987
references: J Neurol Neurosurg Psychiatry. 1960 Nov;23(4):269-82
references: 21610893
references: Brain. 1981 Jun;104(2):217-47
references: 7016254
references: Neurology. 2010 Aug 17;75(7):611-8
references: 20668261
references: Acta Neurol Scand. 1992 Feb;85(2):81-9
references: 1574993
references: Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
references: 12498954
references: Clin Genet. 2013 Jun;83(6):588-90
references: 23017147
references: Neurology. 2011 Apr 5;76(14):1263-9
references: 21464431
references: Nature. 2013 Mar 28;495(7442):467-73
references: 23455423
references: J Neurol Neurosurg Psychiatry. 2013 Sep;84(9):976-81
references: 23418211
references: J Neurol Neurosurg Psychiatry. 2013 Sep;84(9):963-8
references: 23418210
references: J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):995-7
references: 12810805
references: Brain. 2010 Nov;133(11):3470-9
references: 20576696
references: Amyotroph Lateral Scler. 2010 May 3;11(3):289-92
references: 20433412
references: J Neurol Sci. 2010 Jan 15;288(1-2):45-8
references: 19878957