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Amyotrophic lateral sclerosis

Last reviewed: 4 Nov 2023
Last updated: 29 Nov 2023



History and exam

Key diagnostic factors

  • upper extremity weakness
  • stiffness, with poor coordination and balance
  • spastic, unsteady gait
  • painful muscle spasms
  • difficulties arising from chairs and climbing stairs
  • foot drop
  • stiffness and decreased balance with impact on gait
  • head drop
  • progressive difficulties maintaining erect posture, with stooping
  • muscle atrophy
  • increased lumbar lordosis and tendency for abdominal protuberance
  • hyperreflexia
  • dyspnea
  • coughing and choking on liquids (including secretions) and eventually on food
  • strained, slow speech
  • slurred, nasal, and, at times, dysphonic speech
  • hypophonic speech
More key diagnostic factors

Other diagnostic factors

  • propensity for falls
  • sialorrhea and drooling
  • inappropriate bursts of crying or laughing
  • cognitive impairment
  • features of frontotemporal dementia
Other diagnostic factors

Risk factors

  • genetic predisposition or family history
  • age >40 years
  • military service
  • professional athletic activity
  • cigarette smoking
  • agricultural chemical exposure
  • lead exposure
More risk factors

Diagnostic investigations

1st investigations to order

  • clinical diagnosis
More 1st investigations to order

Investigations to consider

  • electromyography (EMG) and nerve conduction studies
  • repetitive nerve stimulation
  • MRI brain and spine
  • anti-GM1 antibodies
  • voltage-gated calcium-channel antibodies
  • acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) antibodies
  • vitamin B₁₂
  • creatine kinase
  • lumbar puncture
  • HIV test
  • genetic testing
More investigations to consider

Treatment algorithm


all patients



Christen Shoesmith, MD, FRCPC

Associate Professor of Neurology

Clinical Neurological Sciences

London Health Sciences Centre





CS has received honoraria from Mitsubishi Tanabe Pharma Canada for participating in scientific medical advisory boards and for presenting at ALS CME events. She has also received stipends for consultancy work for Biogen. She is the chair of the CALS (Canadian ALS Research Network) and in that capacity sits on the scientific medical advisory board for ALS Canada. She is the site PI for several multicenter clinical trials, including trials sponsored by Mitsubishi Tanabe, AL-S Pharma, Sanofi, Calico, and Cytokintetics. CS is an author of references cited in this topic.


Dr Christen Shoesmith would like to gratefully acknowledge Professor Christopher J. McDermott, Dr Laura Simionescu, and Dr Jeremy Shefner, previous contributors to this topic.


CJM received fees for membership of data monitoring committees from Orion Pharma and Orphazyme. LS and JS declare that they have no competing interests.

Peer reviewers

William S. David, MD, PhD

Associate Professor of Neurology

Harvard Medical School




WSD declares that he has no competing interests.

Leo McCluskey, MD MBE

Associate Professor of Neurology

University of Pennsylvania




LM declares that he has no competing interests.

Martin R. Turner, MA, MBBS, PhD, MRCP

MRC/MNDA Lady Edith Wolfson Clinician Scientist & Honorary Consultant Neurologist

Oxford University Department of Clinical Neurology

John Radcliffe Hospital




MRT is a co-author of "Motor Neuron Disease – A Practical Manual" (Oxford University Press, 2010), which is a summary of his own understanding and practice, and which strongly influenced the recommendations for revision of the current article. He receives a proportion of royalties derived from sales of this book.

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