Journal of Neurology

, Volume 252, Issue 12, pp 1435–1447 | Cite as

Diagnostic investigation and multidisciplinary management in motor neuron disease

  • J. A. RochaEmail author
  • C. Reis
  • F. Simões
  • J. Fonseca
  • J. Mendes Ribeiro


Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. ALS is a progressive neurodegenerative disorder, involving motor neurons in the cerebral cortex, brainstem and spinal cord, presenting with a combination of upper and lower motor neuron signs. Etiology remains undetermined, although a multifactorial origin is widely accepted including genetic factors, auto-immunity, oxidative stress, glutamate excitotoxicity and abnormal neurofilament aggregation. The absence of specific diagnostic testing, and variable clinical presentations make the diagnosis of ALS challenging, relying upon correlation of clinical, electrophysiological and neuroimaging data. The disease is relentlessly progressive, with dysarthria, dysphagia, tetraparesis, and respiratory insufficiency due to ongoing respiratory muscle paresis. There is no specific treatment for ALS. Riluzole, a glutamate antagonist, is the only FDA approved drug for ALS, but has only a modest effect on survival. The multiplicity and progressiveness of the disabilities in ALS, highlights the need for a coordinated multidisciplinary rehabilitation program managing symptoms, respiratory care, dysphagia and nutrition, dysarthria and communication, physical and occupational therapy. The main goals are to prolong independence, prevent complications and improve quality of life.

Key words

amyotrophic lateral sclerosis etiopathogenesis motor neuron disease neuroimaging electromyography management rehabilitation 


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  1. 1.
    Donaghy M (1999) Classification and clinical features of motor neuron diseases and motor neuropathies in adults. J Neurol 246:331–333PubMedGoogle Scholar
  2. 2.
    Winderbank A (1994) Adult Motor neuron diseases. In: Munsat TL, Engel AG, Banker BQ (eds) Myology. McGrawHill, New York, pp 1854–1864Google Scholar
  3. 3.
    David C (2002) Electrodiagnostic approach to the patient with suspected motor neuron disease. Neurol Clinics N Am 20:527–555Google Scholar
  4. 4.
    Lou J-S (2004) Amyotrophic lateral sclerosis. In: Gilman S (ed) Neurobase. Arbor Publishing, La Jolla, CAGoogle Scholar
  5. 5.
    Han JJ, et al. (2003) The amyotrophic lateral sclerosis center: A model of multidisciplinary management. Crit Rev Phys Med Rehabil 15:21–40Google Scholar
  6. 6.
    Francis K, Bach JR, DeLisa JA (1999) Evaluation and rehabilitation of patients with adult motor neuron disease. Arch Phys Med Rehabil 80:951–963PubMedCrossRefGoogle Scholar
  7. 7.
    Ross MA (1997) Acquired motor neuron disorders. Neurol Clinics N Am 15:481–500Google Scholar
  8. 8.
    Robberecht W, Van Den Bosch L (1998) The pathogenesis of amyotrophic lateral sclerosis. Neurosci Res Commun 23:67–75CrossRefGoogle Scholar
  9. 9.
    Bryant PR, et al. (2004) Stroke and neurodegenerative disorders. Arch Phys Med Rehabil 85(Suppl 1):21–33CrossRefGoogle Scholar
  10. 10.
    Haverkamp LJ, et al. (1995) Natural history of amyotrophic lateral sclerosis in a database population: validation of a scoring system and a model for survival prediction. Brain 118:707–719PubMedGoogle Scholar
  11. 11.
    Aguila MA, et al. (2003) Prognosis in amyotrophic lateral sclerosis—a population based study. Neurology 60:813–819PubMedGoogle Scholar
  12. 12.
    Leigh PN, et al. (2003) The management of motor neuron disease. J Neurol Neurosurg Psychiatry 74 (Suppl IV):32–47Google Scholar
  13. 13.
    Krakauer MD, Willems PJ, Hofman A (2003) Genetic epidemiology of amyotrophic lateral sclerosis. Clin Genet 63:83–101Google Scholar
  14. 14.
    Rosen DR, Siddique T, Patterson D, et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62PubMedCrossRefGoogle Scholar
  15. 15.
    Cudkowicz ME, McKenna-Vasek D, Sapp PE, et al. (1997) Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Ann Neurol 2:210–221Google Scholar
  16. 16.
    Yang Y, Hentati A, Deng HX, et al. (2001) The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet 29:160–165PubMedCrossRefGoogle Scholar
  17. 17.
    Hand CK, Khoris J, Salachas F, et al. (2001) A novel locus for familial ALS on chromosome 18q. Am J Hum Genet 70(1):251–256PubMedGoogle Scholar
  18. 18.
    Rabin BA, Griffin JW, Crain BJ, Scavina M, Chance PF,Cornblath DR (1999) Autosomal dominant juvenile amyotrophic lateral sclerosis. Brain 122:1539–1550PubMedCrossRefGoogle Scholar
  19. 19.
    Chen YZ, Benett CL, Huynh HM, et al. (2004) DNA/RNA helicase gene mutations in a form of juvenile amyotrophic sclerosis (ALS4). Am J Hum Genet 74:1128–1135PubMedGoogle Scholar
  20. 20.
    Hentati A, Ouahci K, Pericak-Vance MA, Ahmad A, et al. (1997) Linkage of a common locus for recessive amyotrophic lateral sclerosis. Am J Hum Genet A61:A279Google Scholar
  21. 21.
    Hafezparast M, Ahmad-Annuar A, Hummerich H, et al. (2003) Paradigms for identification of new genes in motor neuron degeneration. Amyotroph Lateral Scler Other Motor Neuron Disord 4:249–257PubMedCrossRefGoogle Scholar
  22. 22.
    Hentati A, Ouahci K, Pericak-Vance MA, et al. (1998) Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromossome 15q15-q22 markers. Neurogenetics 2(1):55–60PubMedCrossRefGoogle Scholar
  23. 23.
    Abalkhail H, Mitchell J, Habgood J et al. A new familial amyotrphic lateral sclerosis locus on chromosome 16q12.1–16q12.2. Am J Hum Genet 73:383–389Google Scholar
  24. 24.
    Sapp PC,Hosler BA, McKenna-Yasek D, et al. (2003) Identification of two novel loci for dominantly inherited familial Amyotrophic Lateral Sclerosis. Am J Hum Genet 73:397–403PubMedCrossRefGoogle Scholar
  25. 25.
    Nishimura Al, Mitne-Neto M, Silva MC, et al. (2004) A mutations in the vesicle trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75:822–831PubMedCrossRefGoogle Scholar
  26. 26.
    Hosler BA, Siddique T, Sapp PC, et al. (2000) Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA 284:1664–1669PubMedCrossRefGoogle Scholar
  27. 27.
    Wilhelmsen KC, Lynch T, Pavlou E, Higgins M, Nygaard TG (1994) Localization of disinhibition-dementia parkinsonism amyotrophy complex to 17q21–22. Am J Hum Genet 55:1159–1165PubMedGoogle Scholar
  28. 28.
    Hutton M, Lendon CL, Rizzu P, et al. (1998) Association of missense and 5ƒ-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705PubMedCrossRefGoogle Scholar
  29. 29.
    Munch C, Sedlmeier R, Meyer T, Homberg V, et al. (2004) point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology 63:724–726PubMedGoogle Scholar
  30. 30.
    Storkebaum E, Lambrechts D, Carmeliet P (2004) VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays 26(9):943–954PubMedCrossRefGoogle Scholar
  31. 31.
    Terry PD, Kamel F, Umbach DM, et al. (2004) VEGF promoter haplotype and amyotrophic lateral sclerosis (ALS). J Neurogenet 18:429–434PubMedGoogle Scholar
  32. 32.
    Figlewicz DA, Krizus A, Martinoli MG, et al. (1994) Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Genet 3:1757–1761PubMedGoogle Scholar
  33. 33.
    Corbo M, Hays AP (1992) Peripherin and neurofilament protein coexist in spinal spheroids of motor neuron disease. J Neuropathol Exp Neurol 51:531–537PubMedGoogle Scholar
  34. 34.
    Jackson M, Steers G, Leigh PN, et al. (1999) Polymorphisms in the Glutamate transporter gene EAAT2 in European ALS patients. J Neurol 246:1140–1144PubMedCrossRefGoogle Scholar
  35. 35.
    Carriedo SG, Yin HZ, Weiss JH (1996) Motor neurons are selectively vulnerable to AMPA/kainate receptormediated injury in vitro. J Neurosci 16:4069–4079PubMedGoogle Scholar
  36. 36.
    Lacomblez L, Doppler V, Beucher I, et al. (2002) ApoE: a potential marker of disease progression in ALS. Neurology 58:1112–1114PubMedGoogle Scholar
  37. 37.
    Mui S, Rebeck GW, McKenna-Yasek D, Hyman BT, Brown RH Jr. (1995) Apolipoprotein E epsilon 4 allele is not associated with earlier age at onset in amyotrophic lateral sclerosis. Ann Neurol 38:460–463PubMedCrossRefGoogle Scholar
  38. 38.
    Giess R, Beck M, Goetz R, et al. (2000) Potential role of LIF as a modifier gene in the pathogenesis of amyotrophic lateral sclerosis. Neurology 54:1003–1005PubMedGoogle Scholar
  39. 39.
    Orrell RW, King AW, Lane RJ, de Belleroche JS (1995) Investigation of a null mutation of the CNTF gene in familial amyotrophic lateral sclerosis. J Neurol Sci 132:126–128PubMedCrossRefGoogle Scholar
  40. 40.
    James CM, Daniels J, Wiles CM, Owen MJ (1994) Debrisoquine hydroxylase gene polymorphism in motor neuron disease. Neurodegeneration 3:149–152Google Scholar
  41. 41.
    Olkowski ZL (1998) Mutant AP endonuclease in patients with amyotrophic lateral sclerosis. Neuroreport Jan 26:9(2):239–242Google Scholar
  42. 42.
    Carri MT, et al. (2003) Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals. Brain Res Bull 61:365–374PubMedGoogle Scholar
  43. 43.
    Robert H, Phil B, Robberecht D (2001) Amyotrophic lateral sclerosis: Pathogenesis. Semin Neurol 8:131–139Google Scholar
  44. 44.
    Cudkowicz ME, McKenna-Vasek D, Sapp PE, et al. (1997) Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Ann Neurol 2:210–221Google Scholar
  45. 45.
    Andersen PM, Nilsson P, Keränen M-L, et al. (1997) Phenotypic heterogeneity in MND-patients with CuZn-superoxide dismutase mutations in Scandinavia. Brain 10:1723–1737Google Scholar
  46. 46.
    Andersen MP (2001) Genetics of sporadic ALS. ALS and other motor neuron disorders 2(Suppl 1):S37-S41PubMedGoogle Scholar
  47. 47.
    Rosen DR, Siddiique T, Petterson D, et al. (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362(6415):59–62PubMedCrossRefGoogle Scholar
  48. 48.
    Jan HV, Van den Berg, Wokkle JH (2004) The future of motor neuron disease, the challenges is in the genes. J Neurol 251:491–450Google Scholar
  49. 49.
    Nelson LM, McGuire V, Longstreth WT, et al. (2000) Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption. Am J Epidemiol 151:156–163PubMedGoogle Scholar
  50. 50.
    Weisskopf MG, McCullough ML, Calle EE, et al. (2004) Prospective study of cigarette smoking and amyotrophic lateral sclerosis. Am J Epidemiol 160:26–33PubMedCrossRefGoogle Scholar
  51. 51.
    Louvel E, Hugon J, Doble A (1997) Therapeutic advances in amyotrophic lateral sclerosis. TiPS 18:196–203PubMedGoogle Scholar
  52. 52.
    Barbeito LH (2004) A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Rev 1:12Google Scholar
  53. 53.
    Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW (1995) Selective loss of glial glutamate transporter GLT 1 in amyotrophic lateral sclerosis. Ann Neurol 38:73–84PubMedCrossRefGoogle Scholar
  54. 54.
    Stuerenburg HJ, Kunze K (1998) Tissue nerve growth factor concentrations in neuromuscular diseases. Eur J Neurol 5:487–490PubMedCrossRefGoogle Scholar
  55. 55.
    Georgesco M, Salerno A, Camu W (1997) Somatosensory evoked potentials by stimulation of lower limbs nerves in amyotrophic lateral sclerosis. Electroencephalograph Clin Neurophysiol 104:333–342Google Scholar
  56. 56.
    Haganasi HA, et al. (2002) Cognitive impairment in amyotrophic lateral sclerosis: evidence from neuropsycological investigation and event related potentials. Cogn Brain Res 14:234–244Google Scholar
  57. 57.
    Brooks BR, Miller RG, Swash M, Munsat TL (1998) World Federation of Neurology group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of Amyotrophic sclerosis. Philadelphia: FA Davis, pp 47–64Google Scholar
  58. 58.
    Cornbloth DR, et al. (1992) Nerve conduction studies in amyotrophic sclerosis. Muscle Nerve 15:1111–1115Google Scholar
  59. 59.
    Rowland LP (1998) Diagnosis of amyotrophic lateral scleoris. J Neurol Sci 160(Suppl 1):S6-S24PubMedCrossRefGoogle Scholar
  60. 60.
    Olney RK, Lewis RA, Putnam TD, et al. (2003) Consensus criteria for the diagnosis of multifocal motor neuropathy. Muscle Nerve 27:117–121PubMedCrossRefGoogle Scholar
  61. 61.
    Daube JR (2000) Electrodiagnostic studies in amyotrophic lateral sclerosis and other motor neuron disorders. Muscle Nerve 23:1488–1502PubMedCrossRefGoogle Scholar
  62. 62.
    Masseli RA, Wollman RL, Leung C (1993) Neuromuscular transmission in amyotrophic lateral sclerosis. Muscle Nerve 16:1193–1203Google Scholar
  63. 63.
    Iijima M, Arasaki K, Iwamoto H, et al. (1991) Maximal and minimal motor nerve conduction velocities in patients with motor neuron diseases. Muscle Nerve 14:1110–1115PubMedCrossRefGoogle Scholar
  64. 64.
    Clifford R, et al. (2002) Normal aging, dementia, and neurodegenerative disease-amyotrophic lateral sclerosis. In: Atlas SW (ed) Magnetic resonance imaging of the brain and spine. Lippincott Wand W, Philadelphia, pp 1227–1229Google Scholar
  65. 65.
    Osborn AG (1994) Infection, aquired metabolic,white matter, and degenerative diseases of the brain—amyotrophic lateral sclerosis. In: Osborn AG (ed) Diagnostic Neuroradiology. Mosby, St Louis, pp 778–779Google Scholar
  66. 66.
    Grossman RI, Yousem DM (2003) Neurodegenerative diseases and hydrocephalus-amyotrophic lateral sclerosis. In: Grossman RI, Yousem DM (eds) Neuroradiology—The requisites.Mosby, USA, pp 388–389Google Scholar
  67. 67.
    Comi G, Rovaris M, Leocani L (1999) Neuroimaging in amyotrophic lateral sclerosis. Eur J Neurol 6:629–637PubMedCrossRefGoogle Scholar
  68. 68.
    Bowen BC, et al. (2000) MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis. AJNR 21:647–648PubMedGoogle Scholar
  69. 69.
    Kalra S, et al. (2003) Gabapentin therapy for amyotrophic lateral sclerosis: lack of improvement in neuronal integrity shown by MR spectroscopy. AJNR 24:476–480PubMedGoogle Scholar
  70. 70.
    Ellis CM, et al. (1999) Diffusion tensor MRI assesses corticospinal tract damage in ALS. Neurology 53(5):1051–1058PubMedGoogle Scholar
  71. 71.
    Ulug AM, et al. (1999) Clinical use of Diffusion-Tensor Imaging for diseases causing neuronal and axonal damage. AJNR 20:1044–1048PubMedGoogle Scholar
  72. 72.
    Sundgren PC, et al. (2004) Diffusion tensor imaging of the brain: review of clinical applications. Neuroradiology 46:339–350PubMedCrossRefGoogle Scholar
  73. 73.
    Kato, et al. (1997) Detection of pyramidal tract lesions in amyotrophic lateral sclerosis with magnetization-transfer measurements. AJNR 18:1541–1547PubMedGoogle Scholar
  74. 74.
    Bensimon GL, Lacomblez L, Meininger V (1994) A control trial of riluzole in amyotrophic sclerosis. N Engl J Med 330:585–591PubMedCrossRefGoogle Scholar
  75. 75.
    Borasio GD, et al. (1996) A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I Study Group. J Neurol 243(Suppl 2):26Google Scholar
  76. 76.
    ALS CNTF Treatment Study (ACTS) Phase III (1996) Study Group A double-blind placebo-controlled trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neurology 46:1244–1249Google Scholar
  77. 77.
    Gian Domenico Borasio, Raymond Voltz (1997) Palliative care in amyotrophic lateral sclerosis. J Neurol 244(Suppl 4):S11–S17Google Scholar
  78. 78.
    Ganzini L, Johnston S, Silveira MJ (2002) The final month in patients with ALS. Neurology 59:428–431PubMedGoogle Scholar
  79. 79.
    Lyall RA, Donaldson N, Polkey MI, et al. (2001) Respiratory muscle strength and ventilatory failure in amyotrophic sclerosis. Brain 124(10):2000–2013PubMedCrossRefGoogle Scholar
  80. 80.
    Fitting JW, Paillex R, Hirt L, et al. (1999) Sniff nasal pressure: a sensitive respiratory test to assess progression of amyotrophic lateral sclerosis. Ann Neurol 46(6):887–893PubMedCrossRefGoogle Scholar
  81. 81.
    Morgan RK, McNally S, Alexander M, et al. (2005) Use of sniff-inspiratory force to predict survival in amyotrophic lateral sclerosis. Am J Resp Crit Care Med 171:269–274PubMedGoogle Scholar
  82. 82.
    Miller RG, et al. (1999) “Practice parameter: the care of the patient with amyotrophic lateral sclerosis- an evidence-based review”, American Academy of Neurology-Guidelines for Care in ALSGoogle Scholar
  83. 83.
    Krivickas LS (2000) Symptom management and rehabilitation in ALS. AAEM course handout. Update on Motor Neuron DisGoogle Scholar
  84. 84.
    Bach J (1995) respiratory muscle aids for prevention of morbidity and mortality. Scand Neurol 15:72–83Google Scholar
  85. 85.
    Schiffman PL, Belsh JM (1989) Effect of inspiratory resistance and theophylline on respiratory muscle strength in patients with amyotrophic lateral sclerosis. Am Rev Resp Dis 139:1418–1423PubMedGoogle Scholar
  86. 86.
    Aboussouan LS, Khan SU, Banerjee M, et al. (2001) Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis. Muscle Nerve 24:403–409PubMedCrossRefGoogle Scholar
  87. 87.
    Francis K, DeLisa J (1999) Evaluation and rehabilitation of patients with adult motor neuron disease. Arch Phys Med Rehabil 80:951–963PubMedCrossRefGoogle Scholar
  88. 88.
    Aboussouan LS, Khan SU, Meeker DP, Stelmach K, Mitsumoto H (1997) Effect of non-invasive positive-pressure ventilation on survival im amyotrophic lateral sclerosis. Ann Inter Med 127:450–453Google Scholar
  89. 89.
    Stambler N, Charantan M, Cedarbaum JM (2003) Prognostic indicators of survival in ALS. Neurology 60:1252–1258Google Scholar
  90. 90.
    Kasarskis EJ, Berryman S, et al. (2001) Nutritional status of patients with ALS: relation to proximity of death. Am J Clin Nutr 74:328–334Google Scholar
  91. 91.
    Mazzini L, Corra T, et al. (1995) Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis. Neurology 242:695–698Google Scholar
  92. 92.
    Kasaskis EJ, Scarlata D, Hill R, et al. (1999) A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials. J Neurol Sci 169:118–125Google Scholar
  93. 93.
    Thornton FJ, et al. (2002) Amyotrophic lateral sclerosis: enteral nutrition provision: endoscopic or radiologic gastrostomy? Radiology 224:713–717PubMedGoogle Scholar
  94. 94.
    Drory VE, Goltsman E, Reznik JG (2001) The value of muscle exercise in patients with amyotrophic lateral sclerosis. J Neurol Sci 191:133–137PubMedCrossRefGoogle Scholar
  95. 95.
    Brinkmann JR, Ringel SP (1991) Effectiveness of exercise in progressive neuromuscular disease. J Neurol Rehabil 5:195–199Google Scholar
  96. 96.
    Talbot K (2002) Motor neurone disease. Postgrad Med J 78:513–519PubMedCrossRefGoogle Scholar
  97. 97.
    Oliver D (1996) The quality of care and symptom control-the effects on the terminal phase of MND/ALSJ. Neurol Sc 139(Suppl):134–136Google Scholar
  98. 98.
    World Health organization (1990) Cancer pain relief. Report of the WHO expert comitee. Technical report series 804. Geneva: World Health OrganizationGoogle Scholar
  99. 99.
    Gallagher JP (1989) Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand 80:114–117PubMedCrossRefGoogle Scholar
  100. 100.
    Borasio GD, Miller RG (2001) Clinical Characteristics and Management of ALS Semin Neurol 21(2):155–166PubMedCrossRefGoogle Scholar
  101. 101.
    David Oliver (2002) Paliative care for motor neuron disease. Pract Neurol 2:68–80Google Scholar
  102. 102.
    Schiffer RB, Herndon RM, Rudick RA (1985) Treatment of pathologic laughing and weeping with amitriptyline. N Engl J Med 312:1480–1482PubMedCrossRefGoogle Scholar
  103. 103.
    Borasio GD, Voltz R (1997) Palliative care in amyotrophic lateral sclerosis. J Neurol 244(Suppl 4):S11-S17PubMedGoogle Scholar
  104. 104.
    Iannacone S, Strambi FL (1996) Pharmacological management of emotional lability. Clin Pharmacol 19:532–535Google Scholar
  105. 105.
    Brooks BR, Thisted RA, Appel SH (2004) Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine—A randomized trial. Neurology 63:1364–1370PubMedGoogle Scholar
  106. 106.
    Bushara KO (1997) Sialorrhea in amyotrophic lateral sclerosis: a hypothesis of a new treatment: botulinum A injections of the parotid glands. Med Hypotheses 48:337–339PubMedCrossRefGoogle Scholar
  107. 107.
    Bathia KP, Munchau A, Brown P (1999) Botulinum toxin is a useful treatment in excessive drooling in saliva. J Neurol Neurosurg Psychiatry 667:697Google Scholar
  108. 108.
    Benditt JO, Smith TS, Tonelli MR (2001) Empowering the individual with ALS at the end-of-life: disease-specific advance care planning. Muscle Nerve 24:1706–1709PubMedCrossRefGoogle Scholar
  109. 109.
    Silverstein MD, Stocking CB, Antel JP (1991) Amyotrophic lateral sclerosis and life-sustaining therapy. Mayo Clin Proc 66:906–913PubMedGoogle Scholar
  110. 110.
    Neudert C, Oliver D, Wasner M (2001) The course of the terminal phase in patients with amyotrophic lateral sclerosis. J Neurol 248:612–616PubMedCrossRefGoogle Scholar
  111. 111.
    O’Brien T, Kelly M, Sunders C (1992) Motor neuron disease: a hospice perspective. BMJ 304:471–473PubMedGoogle Scholar
  112. 112.
    Standards and Accreditation Comitee Medical Guidelines Task Force (1996) Medical guidelines for determining prognosis in selected non-cancer diseases. The National Hospice Organization, pp 24–26Google Scholar
  113. 113.
    Krivickas LS, Shocley L, Mitsumoto H (1997) Homecare of patients with amyotrophic lateral sclerosis (ALS). J Neurol Sci 152(Supple 1):S82-S89PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • J. A. Rocha
    • 1
    Email author
  • C. Reis
    • 2
  • F. Simões
    • 3
  • J. Fonseca
    • 2
  • J. Mendes Ribeiro
    • 4
  1. 1.Dept. of Physical Medicine and RehabilitationSenhora da Oliveira HospitalSA GuimarãesPortugal
  2. 2.Dept. of NeuroradiologyS. João HospitalPortoPortugal
  3. 3.Dept. of NeurologyS. João HospitalPortoPortugal
  4. 4.Dept. of NeurophysiologyS. João HospitalPortoPortugal

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