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Semin Neurol 2015; 35(04): 469-476
DOI: 10.1055/s-0035-1558984
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Amyotrophic Lateral Sclerosis: Review

Johnny S. Salameh
1   Department of Neurology, University of Massachusetts Medical School, University of Massachusetts Memorial Medical Center - University Campus, Worcester, Massachusetts
,
Robert H. Brown Jr.
1   Department of Neurology, University of Massachusetts Medical School, University of Massachusetts Memorial Medical Center - University Campus, Worcester, Massachusetts
,
James D. Berry
2   Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
06 October 2015 (online)

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Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting the upper and lower motor neurons. The lifetime risk of developing ALS is estimated at 1:350 for men and 1:500 for women, higher for those who have served in the military. The diagnosis remains clinical with electrodiagnostic support. Alternative diagnoses can usually be ruled out by the use of neuroimaging studies and laboratory evaluation. Perhaps because ALS is a diagnosis of exclusion, there is a substantial delay in diagnosis, upward of 12 months after the onset of symptoms, and most patients see three or more providers in the course of the diagnostic process. Once diagnosed, patients are best medically managed in a multidisciplinary care setting, an approach that has been shown to prolong survival and improve quality of life. Riluzole is the only disease-modifying therapy approved by the Food and Drug Administration, but numerous symptomatic therapies exist. In the past 20 years, ALS has become the focus of intense investigation by a worldwide community of basic scientists, and for clinical investigators the disease is an active area of research, with stem cell therapies, gene therapies, and a host of small molecule agents under investigation at various stages of clinical and preclinical development.

Keywords

amyotrophic lateral sclerosis - motor neuron disease - multidisciplinary care
 

  • References

  • 1 Logroscino G, Traynor BJ, Hardiman O , et al; EURALS. Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry 2008; 79 (1) 6-11
    CrossrefPubMedGoogle Scholar
  • 2 Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V ; Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet 1996; 347 (9013) 1425-1431
    CrossrefPubMedGoogle Scholar
  • 3 Silani V, Messina S, Poletti B , et al. The diagnosis of amyotrophic lateral sclerosis in 2010. Arch Ital Biol 2011; 149 (1) 5-27
    PubMedGoogle Scholar
  • 4 Chiò A, Logroscino G, Hardiman O , et al; Eurals Consortium. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler 2009; 10 (5–6) 310-323
    CrossrefPubMedGoogle Scholar
  • 5 Rowland LP, Mitsumoto H, Przybelski SA. Amyotrophic lateral sclerosis, progressive muscular atrophy, and primary lateral sclerosis. In: Rowland LP, Pedley TA, , eds. Merritt's Neurology. 12th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2010: 802-808
    Google Scholar
  • 6 Brooks BR, Miller RG, Swash M, Munsat TL ; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1 (5) 293-299
    CrossrefPubMedGoogle Scholar
  • 7 Traynor BJ, Codd MB, Corr B, Forde C, Frost E, Hardiman OM. Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: A population-based study. Arch Neurol 2000; 57 (8) 1171-1176
    CrossrefPubMedGoogle Scholar
  • 8 de Carvalho M, Dengler R, Eisen A , et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 2008; 119 (3) 497-503
    CrossrefPubMedGoogle Scholar
  • 9 Paganoni S, Macklin EA, Lee A , et al. Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotroph Lateral Scler Frontotemporal Degener 2014; 15 (5–6) 453-456
    CrossrefPubMedGoogle Scholar
  • 10 Cellura E, Spataro R, Taiello AC, La Bella V. Factors affecting the diagnostic delay in amyotrophic lateral sclerosis. Clin Neurol Neurosurg 2012; 114 (6) 550-554
    CrossrefPubMedGoogle Scholar
  • 11 Williams JR, Fitzhenry D, Grant L, Martyn D, Kerr DA. Diagnosis pathway for patients with amyotrophic lateral sclerosis: retrospective analysis of the US Medicare longitudinal claims database. BMC Neurol 2013; 13: 160
    CrossrefPubMedGoogle Scholar
  • 12 Atassi N, Nakano I, Mora J , et al. Development of a “red flags” symptom list to assist with early recognition and diagnosis of amyotrophic lateral sclerosis. Paper presented at: European Neurological Society June 9-12, 2012; Prague, Czech Republic
    PubMedGoogle Scholar
  • 13 Phukan J, Elamin M, Bede P , et al. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry 2012; 83 (1) 102-108
    CrossrefPubMedGoogle Scholar
  • 14 Arai T, Hasegawa M, Akiyama H , et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 2006; 351 (3) 602-611
    CrossrefPubMedGoogle Scholar
  • 15 Neumann M, Sampathu DM, Kwong LK , et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314 (5796) 130-133
    CrossrefPubMedGoogle Scholar
  • 16 Murphy J, Henry R, Lomen-Hoerth C. Establishing subtypes of the continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007; 64 (3) 330-334
    CrossrefPubMedGoogle Scholar
  • 17 Murphy JM, Henry RG, Langmore S, Kramer JH, Miller BL, Lomen-Hoerth C. Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007; 64 (4) 530-534
    CrossrefPubMedGoogle Scholar
  • 18 Elamin M, Phukan J, Bede P , et al. Executive dysfunction is a negative prognostic indicator in patients with ALS without dementia. Neurology 2011; 76 (14) 1263-1269
    CrossrefPubMedGoogle Scholar
  • 19 Woolley SC, York MK, Moore DH , et al. Detecting frontotemporal dysfunction in ALS: utility of the ALS Cognitive Behavioral Screen (ALS-CBS). Amyotroph Lateral Scler 2010; 11 (3) 303-311
    CrossrefPubMedGoogle Scholar
  • 20 Abrahams S, Newton J, Niven E, Foley J, Bak TH. Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener 2014; 15 (1–2) 9-14
    CrossrefPubMedGoogle Scholar
  • 21 Ravits JM, La Spada AR. ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 2009; 73 (10) 805-811
    CrossrefPubMedGoogle Scholar
  • 22 Grad LI, Pokrishevsky E, Silverman JM, Cashman NR. Exosome-dependent and independent mechanisms are involved in prion-like transmission of propagated Cu/Zn superoxide dismutase misfolding. Prion 2014; 8 (5) 331-335
    CrossrefPubMedGoogle Scholar
  • 23 Grad LI, Yerbury JJ, Turner BJ , et al. Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms. Proc Natl Acad Sci U S A 2014; 111 (9) 3620-3625
    CrossrefPubMedGoogle Scholar
  • 24 Ravits J. Focality, stochasticity and neuroanatomic propagation in ALS pathogenesis. Exp Neurol 2014; 262 (Pt B): 121-126
    CrossrefPubMedGoogle Scholar
  • 25 Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med 2001; 344 (22) 1688-1700
    CrossrefPubMedGoogle Scholar
  • 26 Turner MR, Parton MJ, Shaw CE, Leigh PN, Al-Chalabi A. Prolonged survival in motor neuron disease: a descriptive study of the King's database 1990-2002. J Neurol Neurosurg Psychiatry 2003; 74 (7) 995-997
    CrossrefPubMedGoogle Scholar
  • 27 Kurtzke JF. Epidemiology of amyotrophic lateral sclerosis. Adv Neurol 1982; 36: 281-302
    PubMedGoogle Scholar
  • 28 Wijesekera LC, Mathers S, Talman P , et al. Natural history and clinical features of the flail arm and flail leg ALS variants. Neurology 2009; 72 (12) 1087-1094
    CrossrefPubMedGoogle Scholar
  • 29 Zoccolella S, Beghi E, Palagano G , et al. Predictors of long survival in amyotrophic lateral sclerosis: a population-based study. J Neurol Sci 2008; 268 (1–2) 28-32
    CrossrefPubMedGoogle Scholar
  • 30 Küffner R, Zach N, Norel R , et al. Crowdsourced analysis of clinical trial data to predict amyotrophic lateral sclerosis progression. Nat Biotechnol 2015; 33 (1) 51-57
    PubMedGoogle Scholar
  • 31 Al-Chalabi A, Hardiman O. The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol 2013; 9 (11) 617-628
    CrossrefPubMedGoogle Scholar
  • 32 Worms PM. The epidemiology of motor neuron diseases: a review of recent studies. J Neurol Sci 2001; 191 (1–2) 3-9
    CrossrefPubMedGoogle Scholar
  • 33 Huisman MH, de Jong SW, van Doormaal PT , et al. Population based epidemiology of amyotrophic lateral sclerosis using capture-recapture methodology. J Neurol Neurosurg Psychiatry 2011; 82 (10) 1165-1170
    CrossrefPubMedGoogle Scholar
  • 34 Weisskopf MG, O'Reilly EJ, McCullough ML , et al. Prospective study of military service and mortality from ALS. Neurology 2005; 64 (1) 32-37
    CrossrefPubMedGoogle Scholar
  • 35 Armon C. Smoking may be considered an established risk factor for sporadic ALS. Neurology 2009; 73 (20) 1693-1698
    CrossrefPubMedGoogle Scholar
  • 36 Abel EL. Football increases the risk for Lou Gehrig's disease, amyotrophic lateral sclerosis. Percept Mot Skills 2007; 104 (3 Pt 2): 1251-1254
    PubMedGoogle Scholar
  • 37 Chiò A, Benzi G, Dossena M, Mutani R, Mora G. Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 2005; 128 (Pt 3) 472-476
    CrossrefPubMedGoogle Scholar
  • 38 Al-Chalabi A, Leigh PN. Trouble on the pitch: are professional football players at increased risk of developing amyotrophic lateral sclerosis?. Brain 2005; 128 (Pt 3) 451-453
    CrossrefPubMedGoogle Scholar
  • 39 Hamidou B, Couratier P, Besançon C, Nicol M, Preux PM, Marin B. Epidemiological evidence that physical activity is not a risk factor for ALS. Eur J Epidemiol 2014; 29 (7) 459-475
    CrossrefPubMedGoogle Scholar
  • 40 Pupillo E, Messina P, Giussani G , et al; EURALS Consortium. Physical activity and amyotrophic lateral sclerosis: a European population-based case-control study. Ann Neurol 2014; 75 (5) 708-716
    CrossrefPubMedGoogle Scholar
  • 41 Turner MR, Abisgold J, Yeates DG, Talbot K, Goldacre MJ. Head and other physical trauma requiring hospitalisation is not a significant risk factor in the development of ALS. J Neurol Sci 2010; 288 (1–2) 45-48
    CrossrefPubMedGoogle Scholar
  • 42 McKee AC, Gavett BE, Stern RA , et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol 2010; 69 (9) 918-929
    CrossrefPubMedGoogle Scholar
  • 43 O'Reilly EJ, Wang H, Weisskopf MG , et al. Premorbid body mass index and risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14 (3) 205-211
    CrossrefPubMedGoogle Scholar
  • 44 Leblond CS, Kaneb HM, Dion PA, Rouleau GA. Dissection of genetic factors associated with amyotrophic lateral sclerosis. Exp Neurol 2014; 262 (Pt B): 91-101
    CrossrefPubMedGoogle Scholar
  • 45 Sreedharan J, Brown Jr RH. Amyotrophic lateral sclerosis: problems and prospects. Ann Neurol 2013; 74 (3) 309-316
    CrossrefPubMedGoogle Scholar
  • 46 Peters OM, Ghasemi M, Brown Jr RH. Emerging mechanisms of molecular pathology in ALS. J Clin Invest 2015; 125 (6) 2548
    PubMedGoogle Scholar
  • 47 DeJesus-Hernandez M, Mackenzie IR, Boeve BF , et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011; 72 (2) 245-256
    CrossrefPubMedGoogle Scholar
  • 48 Gijselinck I, Van Langenhove T, van der Zee J , et al. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol 2012; 11 (1) 54-65
    CrossrefPubMedGoogle Scholar
  • 49 Renton AE, Majounie E, Waite A , et al; ITALSGEN Consortium. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011; 72 (2) 257-268
    CrossrefPubMedGoogle Scholar
  • 50 Rosen DR, Siddique T, Patterson D , et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362 (6415) 59-62
    CrossrefPubMedGoogle Scholar
  • 51 Andersen PM, Nilsson P, Ala-Hurula V , et al. Amyotrophic lateral sclerosis associated with homozygosity for an Asp90Ala mutation in CuZn-superoxide dismutase. Nat Genet 1995; 10 (1) 61-66
    CrossrefPubMedGoogle Scholar
  • 52 Sreedharan J, Blair IP, Tripathi VB , et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319 (5870) 1668-1672
    CrossrefPubMedGoogle Scholar
  • 53 Kwiatkowski Jr TJ, Bosco DA, Leclerc AL , et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 2009; 323 (5918) 1205-1208
    CrossrefPubMedGoogle Scholar
  • 54 Smith BN, Vance C, Scotter EL , et al. Novel mutations support a role for Profilin 1 in the pathogenesis of ALS. Neurobiol Aging 2015; 36 (3) 1602.e17-1602.e27
    CrossrefPubMedGoogle Scholar
  • 55 Pensato V, Tiloca C, Corrado L , et al; SLAGEN Consortium. TUBA4A gene analysis in sporadic amyotrophic lateral sclerosis: identification of novel mutations. J Neurol 2015; 262 (5) 1376-1378
    CrossrefPubMedGoogle Scholar
  • 56 Johnson JO, Mandrioli J, Benatar M , et al; ITALSGEN Consortium. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 2010; 68 (5) 857-864
    CrossrefPubMedGoogle Scholar
  • 57 González-Pérez P, Cirulli ET, Drory VE , et al. Novel mutation in VCP gene causes atypical amyotrophic lateral sclerosis. Neurology 2012; 79 (22) 2201-2208
    CrossrefPubMedGoogle Scholar
  • 58 Kim HJ, Kim NC, Wang YD , et al. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 2013; 495 (7442) 467-473
    CrossrefPubMedGoogle Scholar
  • 59 Mitchell J, Paul P, Chen HJ , et al. Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase. Proc Natl Acad Sci U S A 2010; 107 (16) 7556-7561
    CrossrefPubMedGoogle Scholar
  • 60 Greenway MJ, Andersen PM, Russ C , et al. ANG mutations segregate with familial and ‘sporadic’ amyotrophic lateral sclerosis. Nat Genet 2006; 38 (4) 411-413
    CrossrefPubMedGoogle Scholar
  • 61 Van Hoecke A, Schoonaert L, Lemmens R , et al. EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans. Nat Med 2012; 18 (9) 1418-1422
    CrossrefPubMedGoogle Scholar
  • 62 Cirulli ET, Lasseigne BN, Petrovski S , et al; FALS Sequencing Consortium. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 2015; 347 (6229) 1436-1441
    CrossrefPubMedGoogle Scholar
  • 63 Freischmidt A, Wieland T, Richter B , et al. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci 2015; 18 (5) 631-636
    CrossrefPubMedGoogle Scholar
  • 64 Traynor BJ, Alexander M, Corr B, Frost E, Hardiman O. Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. J Neurol Neurosurg Psychiatry 2003; 74 (9) 1258-1261
    CrossrefPubMedGoogle Scholar
  • 65 Van den Berg JP, Kalmijn S, Lindeman E , et al. Multidisciplinary ALS care improves quality of life in patients with ALS. Neurology 2005; 65 (8) 1264-1267
    CrossrefPubMedGoogle Scholar
  • 66 Miller RG, Jackson CE, Kasarskis EJ , et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009; 73 (15) 1227-1233
    CrossrefPubMedGoogle Scholar
  • 67 Miller RG, Jackson CE, Kasarskis EJ , et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009; 73 (15) 1218-1226
    CrossrefPubMedGoogle Scholar
  • 68 Andersen PM, Borasio GD, Dengler R , et al; EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis. EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol 2005; 12 (12) 921-938
    CrossrefPubMedGoogle Scholar
  • 69 Bensimon G, Lacomblez L, Meininger V ; ALS/Riluzole Study Group. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 1994; 330 (9) 585-591
    CrossrefPubMedGoogle Scholar
  • 70 Lacomblez L, Bensimon G, Leigh PN , et al; ALS/Riluzole Study Group-II. A confirmatory dose-ranging study of riluzole in ALS. Neurology 1996; 47 (6) (Suppl. 04) S242-S250
    CrossrefPubMedGoogle Scholar
  • 71 Tavakoli M. Disease progression in amyotrophic lateral sclerosis. Identifying the cost-utility of riluzole by disease stage. Eur J Health Econ 2002; 3 (3) 156-165
    CrossrefPubMedGoogle Scholar
  • 72 Groeneveld GJ, van Kan HJ, Lie-A-Huen L, Guchelaar HJ, van den Berg LH. An association study of riluzole serum concentration and survival and disease progression in patients with ALS. Clin Pharmacol Ther 2008; 83 (5) 718-722
    CrossrefPubMedGoogle Scholar
  • 73 Bensimon G, Lacomblez L, Delumeau JC, Bejuit R, Truffinet P, Meininger V ; Riluzole/ALS Study Group II. A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis. J Neurol 2002; 249 (5) 609-615
    CrossrefPubMedGoogle Scholar
  • 74 Rudnicki SA. Factors influencing a patient's decision regarding riluzole: an early experience. J Neurol Sci 1997; 152 (Suppl. 01) S80-S81
    CrossrefPubMedGoogle Scholar
  • 75 Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2012; 3: CD001447
    PubMedGoogle Scholar
  • 76 Brooks BR, Thisted RA, Appel SH , et al; AVP-923 ALS Study Group. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004; 63 (8) 1364-1370
    CrossrefPubMedGoogle Scholar
  • 77 Pioro EP, Brooks BR, Cummings J , et al; Safety, Tolerability, and Efficacy Results Trial of AVP-923 in PBA Investigators. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol 2010; 68 (5) 693-702
    CrossrefPubMedGoogle Scholar
  • 78 Ho DT, Ruthazer R, Russell JA. Shoulder pain in amyotrophic lateral sclerosis. J Clin Neuromuscul Dis 2011; 13 (1) 53-55
    CrossrefPubMedGoogle Scholar
  • 79 Desport JC, Preux PM, Truong CT, Courat L, Vallat JM, Couratier P. Nutritional assessment and survival in ALS patients. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1 (2) 91-96
    CrossrefPubMedGoogle Scholar
  • 80 Reich-Slotky R, Andrews J, Cheng B , et al. Body mass index (BMI) as predictor of ALSFRS-R score decline in ALS patients. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14 (3) 212-216
    CrossrefPubMedGoogle Scholar
  • 81 Shimizu T, Nagaoka U, Nakayama Y , et al. Reduction rate of body mass index predicts prognosis for survival in amyotrophic lateral sclerosis: a multicenter study in Japan. Amyotroph Lateral Scler 2012; 13 (4) 363-366
    CrossrefPubMedGoogle Scholar
  • 82 Marin B, Desport JC, Kajeu P , et al. Alteration of nutritional status at diagnosis is a prognostic factor for survival of amyotrophic lateral sclerosis patients. J Neurol Neurosurg Psychiatry 2011; 82 (6) 628-634
    CrossrefPubMedGoogle Scholar
  • 83 Aydogdu I, Tanriverdi Z, Ertekin C. Dysfunction of bulbar central pattern generator in ALS patients with dysphagia during sequential deglutition. Clin Neurophysiol 2011; 122 (6) 1219-1228
    CrossrefPubMedGoogle Scholar
  • 84 Kasarskis EJ, Scarlata D, Hill R, Fuller C, Stambler N, Cedarbaum JM. A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials. J Neurol Sci 1999; 169 (1–2) 118-125
    CrossrefPubMedGoogle Scholar
  • 85 Desport JC, Mabrouk T, Bouillet P, Perna A, Preux PM, Couratier P. Complications and survival following radiologically and endoscopically-guided gastrostomy in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2005; 6 (2) 88-93
    CrossrefPubMedGoogle Scholar
  • 86 Mitsumoto H, Davidson M, Moore D , et al; ALS CARE Study Group. Percutaneous endoscopic gastrostomy (PEG) in patients with ALS and bulbar dysfunction. Amyotroph Lateral Scler Other Motor Neuron Disord 2003; 4 (3) 177-185
    CrossrefPubMedGoogle Scholar
  • 87 Shaw AS, Ampong MA, Rio A , et al. Survival of patients with ALS following institution of enteral feeding is related to pre-procedure oximetry: a retrospective review of 98 patients in a single centre. Amyotroph Lateral Scler 2006; 7 (1) 16-21
    PubMedGoogle Scholar
  • 88 Spataro R, Ficano L, Piccoli F, La Bella V. Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: effect on survival. J Neurol Sci 2011; 304 (1–2) 44-48
    CrossrefPubMedGoogle Scholar
  • 89 Atassi N, Cudkowicz ME, Schoenfeld DA. Advanced statistical methods to study the effects of gastric tube and non-invasive ventilation on functional decline and survival in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2011; 12 (4) 272-277
    CrossrefPubMedGoogle Scholar
  • 90 Martin L, Blomberg J, Lagergren P. Patients' perspectives of living with a percutaneous endoscopic gastrostomy (PEG). BMC Gastroenterol 2012; 12: 126
    Google Scholar
  • 91 Rio A, Ellis C, Shaw C , et al. Nutritional factors associated with survival following enteral tube feeding in patients with motor neurone disease. J Hum Nutr Diet 2010; 23 (4) 408-415
    CrossrefPubMedGoogle Scholar
  • 92 Thurman DJ, Stevens JA, Rao JK ; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: assessing patients in a neurology practice for risk of falls (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2008; 70 (6) 473-479
    CrossrefPubMedGoogle Scholar
  • 93 Gil J, Funalot B, Verschueren A , et al. Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study. Eur J Neurol 2008; 15 (11) 1245-1251
    CrossrefPubMedGoogle Scholar
  • 94 Green JR, Yunusova Y, Kuruvilla MS , et al. Bulbar and speech motor assessment in ALS: challenges and future directions. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14 (7–8) 494-500
    CrossrefPubMedGoogle Scholar
  • 95 Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 2006; 5 (2) 140-147
    CrossrefPubMedGoogle Scholar
  • 96 Pinto AC, Evangelista T, Carvalho M, Alves MA, Sales Luís ML. Respiratory assistance with a non-invasive ventilator (Bipap) in MND/ALS patients: survival rates in a controlled trial. J Neurol Sci 1995; 129 (Suppl): 19-26
    CrossrefPubMedGoogle Scholar
  • 97 Miller TM, Smith RA, Kordasiewicz H, Kaspar BK. Gene-targeted therapies for the central nervous system. Arch Neurol 2008; 65 (4) 447-451
    CrossrefPubMedGoogle Scholar