Download PDF
Semin Neurol 2001; 21(2): 155-166
DOI: 10.1055/s-2001-15268
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Clinical Characteristics and Management of ALS

Gian Domenico Borasio1 , Robert G. Miller2
  • 1Department of Neurology and Interdisciplinary Palliative Care Unit, University of Munich, München, Germany and
  • 2Department of Neurology and The Forbes Norris MDA/ALS Center, California Pacific Medical Center, San Francisco, California
Further Information

Publication History

Publication Date:
31 December 2001 (online)

    Permissions and Reprints

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor neuron disease in adulthood. The clinical picture was accurately described by Charcot over 125 years ago and consists of generalized fasciculations, progressive atrophy and weakness of the skeletal muscles, spasticity and pyramidal tract signs, dysarthria, dysphagia, and dyspnea. Pseudobulbar affect is common. Disease-specific treatment options are still unsatisfactory. However, therapeutic nihilism is not justified as a large array of palliative measures is available to enhance the quality of life of patients and their families. Palliative care in ALS is a multidisciplinary effort requiring careful coordination. An open and frank disclosure of the diagnosis is of paramount importance. Nutritional deficiency due to pronounced dysphagia can be relieved by a percutaneous endoscopic gastrostomy. Respiratory insufficiency can be effectively treated by noninvasive home mechanical ventilation. The terminal phase of the disease should be discussed, at the latest, when symptoms of dyspnea appear in order to prevent unwarranted fears of ``choking to death.'' Collaboration with hospice and completion of advance directives can be of invaluable help in the terminal phase.

KEYWORD

Amyotrophic lateral sclerosis - motor neuron disease - antiglutamatergic agents - symptom control - noninvasive ventilation - palliative care

REFERENCES

  • 1 Charcot J M. De la sclérose latérale amyotrophique.  Prog Med . 1874;  2 325-327 341-342 453-455
    PubMedGoogle Scholar
  • 2 Kondo K. Epidemiology of motor neuron disease. In: Leigh PN, Swash M, eds. Motor Neuron Disease: Biology and Management New York: Springer Verlag 1995: 19-33
    Google Scholar
  • 3 Lilienfeld D E, Chan E, Ehland J. Rising mortality from motoneuron disease in the USA 1962-1984.  Lancet . 1989;  1 710-713
    PubMedGoogle Scholar
  • 4 Gubbay S S, Kahana E, Zilber N. Amyotrophic lateral sclerosis: a study of its presentation and prognosis.  J Neurol . 1985;  232 295-300
    PubMedGoogle Scholar
  • 5 Juergens S M, Kurland L T. Epidemiology. In: Mulder DW, ed. The Diagnosis and Treatment of Amyotrophic Lateral Sclerosis Boston: Houghton Mifflin 1980: 35-46
    Google Scholar
  • 6 Norris F, Shepherd R, Denys E. Onset, natural history and outcome in idiopathic adult motor neuron disease.  J Neurol Sci . 1993;  118 48-55
    CrossrefPubMedGoogle Scholar
  • 7 Haverkamp L J, Appel V, Appel S H. Natural history of amyotrophic lateral sclerosis in a database population: validation of a scoring system and a model for survival prediction.  Brain . 1995;  118 707-719
    CrossrefPubMedGoogle Scholar
  • 8 Li T M, Alberman E, Swash M. Clinical associations of 560 cases of motor neuron disease.  J Neurol Neurosurg Psychiatry . 1990;  51 778-784
    PubMedGoogle Scholar
  • 9 Küther G, Struppler A. Dynamic aspects of the degenerative process in amyotrophic lateral sclerosis: a clinical and electromyographical study. In: Dengler R, ed. The Motor Unit: Physiology, Diseases, Regeneration Munich: Urban & Schwarzenberg 1990: 76-82
    Google Scholar
  • 10 Appel V, Stewart S S, Smith G, Appel S H. A rating scale for amyotrophic lateral sclerosis: description and preliminary experience.  Ann Neurol . 1978;  22 328-333
    PubMedGoogle Scholar
  • 11 Mulder D W, Howard R M. Patient resistance and prognosis in amyotrophic lateral sclerosis.  Mayo Clin Proc . 1976;  51 537-541
    PubMedGoogle Scholar
  • 12 Grohme K, von Maravic M, Gasser T, Borasio G D. A case of amyotrophic lateral sclerosis with a very slow progression over 44 years.  Neuromuscul Disord . 1998;  11 414-416
    PubMedGoogle Scholar
  • 13 Caroscio J T, Calhoun W F, Yahr M D. Prognostic factors in motor neuron disease: a prospective study of survival. In: Rose FC, ed. Research Progress in Motor Neuron Diseases Bath: Pitman 1984: 34-43
    Google Scholar
  • 14 Hirano A, Iwata M. Pathology of motor neurons with special reference to amyotrophic lateral sclerosis and related diseases. In: Tsubaki T, Toyokura Y, eds. Amyotrophic Lateral Sclerosis Baltimore: University Park Press 1978: 107-133
    Google Scholar
  • 15 Kolde G, Bachus R, Ludolph A C. Skin involvement in amyotrophic lateral sclerosis.  Lancet . 1996;  347 1226-1227
    CrossrefPubMedGoogle Scholar
  • 16 Louwerse E S, Sillevis Smitt A E P, de Jong J B V M. Differential diagnosis of sporadic amyotrophic lateral sclerosis, progressive spinal muscular atrophy and progressive bulbar palsy in adults. In: Klawans HL, Vinken PJ, Bruyn GW, de Jong JMBV, eds. Handbook of Clinical Neurology, Vol 59, Diseases of the Motor System. Amsterdam: North Holland 1991: 383-424
    Google Scholar
  • 17 Brooks B R. Diagnostic dilemmas in amyotrophic lateral sclerosis.  J Neurol Sci . 1999;  S1-S9 (S1-S9)
    PubMedGoogle Scholar
  • 18 Brooks B R. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis.  J Neurol Sci . 1994;  96-107 (96-107)
    PubMedGoogle Scholar
  • 19 Brooks B R, Miller R G, Swash M, Munsat T. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. World Federation of Neurology Subcommittee of Motor Neuron Disease Available at: www.wfnals.org/Articles/elescorial1998.htm. Accessed April 22 2001
    Google Scholar
  • 20 Gordon P H, Rowland L P, Younger D S. Lymphoproliferative disorders and motor neuron disease: an update.  Neurology . 1997;  48 1671-1678
    PubMedGoogle Scholar
  • 21 Forsyth P A, Dalmau J, Graus F. Motor neuron syndromes in cancer patients.  Ann Neurol . 1997;  41 722-730
    CrossrefPubMedGoogle Scholar
  • 22 Rosen D R, Siddique T, Patterson D. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.  Nature . 1993;  362 59-62
    CrossrefPubMedGoogle Scholar
  • 23 Figlewicz D A, McKenna-Yasek D, Horvitz R, Rouleau G A, Brown R H. Epidemiological analysis of 90 families with hereditary amyotrophic lateral sclerosis.  Int ALS-MND Update . 1989;  9-10
    PubMedGoogle Scholar
  • 24 Gurney M E, Cutting F B, Zhai P. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis.  Ann Neurol . 1996;  39 147-157
    CrossrefPubMedGoogle Scholar
  • 25 Klivenyi P, Ferrante R J, Matthews R T. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.  Nat Med . 1990;  5 347-350
    PubMedGoogle Scholar
  • 26 Anonymous. ACMG/ASHG statement. Laboratory guidelines for Huntington disease genetic testing. The American College of Medical Genetics/American Society of Human Genetics Huntington Disease Genetic Testing Working Group.  Am J Hum Genet . 1998;  62 1243-1247
    CrossrefPubMedGoogle Scholar
  • 27 Lacomblez L, Bensimon G, Leigh P N, Guillet P, Meininger V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis.  Lancet . 1996;  347 1425-1431
    CrossrefPubMedGoogle Scholar
  • 28 Anonymous. Practice advisory on the treatment of amyotrophic lateral sclerosis with riluzole: report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology . 1997;  49 657-659
    PubMedGoogle Scholar
  • 29 Miller R G, Rosenberg J A, Gelinas D F, et a l, and the ALS Practice Parameters Task Force. Practice Parameter. The care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology . 1999;  52 1311-1323
    PubMedGoogle Scholar
  • 30 Doyle D, O'Connell S. Breaking bad news: starting palliative care.  J R Soc Med . 1996;  89 590-591
    PubMedGoogle Scholar
  • 31 O'Brien T. Palliative care and taboos within motor neurone disease.  Palliat Med . 1993;  69-72 (69-72)
    PubMedGoogle Scholar
  • 32 Meininger V. Breaking bad news in amyotrophic lateral sclerosis.  Palliat Med . 1993;  37-40 (37-40)
    PubMedGoogle Scholar
  • 33 Borasio G D, Sloan R, Pongratz D E. Breaking the news in amyotrophic lateral sclerosis.  J Neurol Sci . 1998;  S127-S133 (S127-S133)
    PubMedGoogle Scholar
  • 34 O'Brien T, Kelly M, Saunders C. Motor neuron disease: a hospice perspective.  Br Med J . 1992;  304 471-473
    PubMedGoogle Scholar
  • 35 Hayashi H, Shuuichi K, Kawada A. Amyotrophic lateral sclerosis patients living beyond respiratory failure.  J Neurol Sci . 1991;  105 73-78
    CrossrefPubMedGoogle Scholar
  • 36 Silverstein M D, Stocking C B, Antel J P. Amyotrophic lateral sclerosis and life-sustaining therapy: patients' desires for information, participation in decision making, and life-sustaining therapy.  Mayo Clin Proc . 1991;  66 906-913
    PubMedGoogle Scholar
  • 37 Raischl J, Hirsch B, Bausewein C, Borasio G D. Hospice care for ALS patients in Germany: the Munich experience. Proceedings of the 9th International Symposium on ALS/MND Munich: International Alliance of ALS/MND Associations; 1998
    Google Scholar
  • 38 Marquardt G, Lorenz R. Intrathecal baclofen for intractable spasticity in amyotrophic lateral sclerosis.  J Neurol . 1999;  246 619-620
    PubMedGoogle Scholar
  • 39 Smith R A, Gillie E, Licht J. Palliative treatment of motor neuron disease. In: de Jong JMBV, ed. Handbook of Clinical Neurology, Vol 15, Diseases of the Motor System. New York: Elsevier 1991: 459-473
    Google Scholar
  • 40 Mathus-Vliegen L M, Louwerse L S, Merkus M P, Tytgat G N, de Jong J B V M. Percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis and impaired pulmonary function.  Gastrointest Endosc . 1994;  40 463-469
    PubMedGoogle Scholar
  • 41 Mazzini L, Corra T, Zaccala M. Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis.  J Neurol . 1995;  242 695-698
    PubMedGoogle Scholar
  • 42 Moss A H, Casey P, Stocking C B. Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family, and physician attitudes.  Neurology . 1993;  43 438-443
    CrossrefPubMedGoogle Scholar
  • 43 Cazzolli P A, Oppenheimer E A. Home mechanical ventilation for amyotrophic lateral sclerosis: nasal compared to tracheostomy-intermittent positive pressure ventilation.  J Neurol Sci . 1996;  123-128 (123-128)
    PubMedGoogle Scholar
  • 44 Aboussouan L S, Khan S U, Meeker D P, Stelmach K, Mitsumoto H. Effect of noninvasive positive-pressure ventilation on survival in amyotrophic lateral sclerosis.  Ann Intern Med . 1997;  127 450-453
    PubMedGoogle Scholar
  • 45 Oppenheimer E A. Decision-making in the respiratory care of amyotrophic lateral sclerosis patients: should home mechanical ventilation be used?.  Palliat Med . 1993;  49-64 (49-64)
    PubMedGoogle Scholar
  • 46 Voltz R, Borasio G D. Palliative therapy in the terminal stage of neurologic disease.  J Neurol . 1997;  S2-S10 (S2-S10)
    PubMedGoogle Scholar
  • 47 Goldblatt D, Greenlaw J. Starting and stopping the ventilator for patients with amyotrophic lateral sclerosis.  Neurol Clin . 1989;  7 789-806
    PubMedGoogle Scholar
  • 48 Borasio G D, Voltz R. Discontinuation of life support in patients with amyotrophic lateral sclerosis.  J Neurol . 1998;  245 717-722
    CrossrefPubMedGoogle Scholar
  • 49 Caroscio J T, Cohen J A, Gudesblatt M. Amitriptyline in amyotrophic lateral sclerosis.  N Engl J Med . 1985;  313 1478
    PubMedGoogle Scholar
  • 50 Gallagher J P. Pathologic laughter and crying in ALS: a search for their origin.  Acta Neurol Scand . 1989;  80 114-117
    CrossrefPubMedGoogle Scholar
  • 51 Schiffer R B, Cash J, Herndon R M. Treatment of emotional lability with low-dosage tricyclic antidepressants.  Psychosomatics . 1983;  24 1094-1096
    PubMedGoogle Scholar
  • 52 Poeck K. Pathologisches Lachen und Weinen bei bulbärer myatrophischer Lateralsklerose.  Dtsch Med Wochenschr . 1996;  94 310-314
    PubMedGoogle Scholar
  • 53 Schiffer R B, Herndon R M, Rudick R A. Treatment of pathologic laughing and weeping with amitriptyline.  N Engl J Med . 1985;  312 1480-1482
    PubMedGoogle Scholar
  • 54 Iannaccone S, Ferini-Strambi L. Pharmacologic treatment of emotional lability.  Clin Neuropharmacol . 1996;  19 532-535
    PubMedGoogle Scholar
  • 55 Sieb J P, Jerusalem F, Fresmann J. Symptomatische Therapie bei amyotrophischer Lateralsklerose.  Dtsch Med Wochenschr . 1987;  112 769-772
    PubMedGoogle Scholar
  • 56 Norris F H, Smith R A, Denis E H. Motor neuron disease: towards better care.  Br Med J . 1985;  291 259-262
    PubMedGoogle Scholar
  • 57 McDonald E R, Wiedenfeld S A, Hillel A, Carpenter C L, Walter R A. Survival in amyotrophic lateral sclerosis: the role of psychological factors.  Arch Neurol . 1994;  51 17-23
    PubMedGoogle Scholar
  • 58 Brodtkorb E, Wyzocka-Bakowska M M, Lillevold P E. Transdermal scopolamine in drooling.  J Ment Defic Res . 1988;  32 233-237
    PubMedGoogle Scholar
  • 59 Camp-Bruno J A, Winsberg B G, Green-Parsons A R, Abrams J P. Efficacy of benztropine therapy for drooling.  Dev Med Child Neurol . 1989;  31 309-319
    CrossrefPubMedGoogle Scholar
  • 60 Reddihough D, Johnson H, Staples M, Hudson I, Exarchos H. Use of trihexyphenidyl hydrochloride to control drooling of children with cerebral palsy.  Dev Med Child Neurol . 1990;  32 985-989
    PubMedGoogle Scholar
  • 61 Lewis D W, Fontana C, Mehallick L K, Everett Y. Transdermal scopolamine for reductions in drooling in developmentally delayed children.  Dev Med Child Neurol . 1994;  36 484-486
    PubMedGoogle Scholar
  • 62 Blasco P A, Stansbury J CK. Glycopyrrolate treatment of chronic drooling.  Arch Pediatr Adolesc Med . 1996;  150 932-935
    CrossrefPubMedGoogle Scholar
  • 63 Stern L M. Preliminary study of glycopyrrolate in the management of drooling.  J Paediatr Child Health . 1997;  33 52-54
    PubMedGoogle Scholar
  • 64 Janzen V D, Rae R, Hudson A J. Otolaryngologic manifestations of amyotrophic lateral sclerosis.  J Otolaryngol . 1988;  17 41-42
    PubMedGoogle Scholar
  • 65 Robinson A CR, Khoury G G, Robinson P M. Role of irradiation in the suppression of parotid secretions.  J Laryngol Otol . 1989;  103 594-595
    PubMedGoogle Scholar
  • 66 Bach J R. Mechanical insufflation-exsufflation: comparison of peak expiratory flows with manually assisted and unassisted coughing techniques.  Chest . 1993;  104 1553-1562
    CrossrefPubMedGoogle Scholar
  • 67 Bach J R, Smith W H, Michaels J. Airway secretion clearance by mechanical exsufflation for postpoliomyelitis ventilator assisted individuals.  Arch Phys Med Rehabil . 1993;  74 170-177
    PubMedGoogle Scholar
  • 68 Gelinas D, Miller R G. A treatable disease: a guide to the management of amyotrophic lateral sclerosis. In: Brown RH Jr, Meininger V, Swash M, eds. Amyotrophic Lateral Sclerosis London: Martin Dunitz; 2000: 405-421
    Google Scholar
  • 69 Oliver D. Motor Neurone Disease.  London: Royal College of General Practitioners; 1994
    Google Scholar
  • 70 Newrick P G, Langton-Hewer R. Pain in motor neuron disease.  J Neurol Neurosurg Psychiatry . 1985;  48 838-840
    PubMedGoogle Scholar
  • 71 World Health Organization. Cancer Pain Relief and Palliative Care: Report of a WHO Expert Committee Geneva: World Health Organization; 1990
  • 72 Neudert C, Oliver D, Wasner M, Borasio G D. The course of the terminal phase in patients with amyotrophic lateral sclerosis.  J Neurol. In press .
    PubMedGoogle Scholar
  • 73 Oliver D. The quality of care and symptom control: the effects on the terminal phase of ALS/MND.  J Neurol Sci . 1996;  134-136 (134-136)
    PubMedGoogle Scholar
  • 74 Wilbourn A J, Mitsumoto H. Why are patients with amyotrophic lateral sclerosis so nice?. Proceedings of the 9th International Symposium on ALS/MND Munich: International Alliance of ALS/MND Associations; 1998
    Google Scholar
  • 75 Borasio G D. Amyotrophic lateral sclerosis: lessons in trial design from recent trials.  J Neurol Sci . 1997;  S23-S28 (S23-S28)
    PubMedGoogle Scholar
  • 76 Giess R, Naumann M, Werner E. Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis.  J Neurol Neurosurg Psychiatry . 2000;  69 121-123
    Google Scholar
      >