Progressive disease characterised by degeneration of the motor neurons with cortical, brainstem, and ventral cord locations.
Usually presents as a combination of upper motor neuron and lower motor neuron symptoms and signs, involving initially 1 segment of the neuroaxis (i.e., cranial, cervical, thoracic, or lumbosacral), and then progressively spreading typically to contiguous areas.
Typical presentations include limb-onset and bulbar-onset ALS, and, less frequently, respiratory-onset ALS. Generalisation of the symptoms follows in time, without intervals of remission, exacerbation, or stabilisation, resulting in progressive disability and death.
There is no cure for ALS at the present time. The focus of medical care is to provide supportive and palliative intervention, aiming to improve the quality of life for patients. Riluzole is used for modifying the disease course and should be offered to patients at the time of diagnosis.
Continued discussions regarding advance directives, as well as methods of respiratory and nutritional support are critical; palliative care options should also be presented and discussed prior to the need for their initiation.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterised by progressive muscle weakness that can start in limb, axial, bulbar, or respiratory muscles and then generalises relentlessly, causing progressive disability and ultimately death, usually from respiratory failure.
History and exam
Key diagnostic factors
- presence of risk factors
- upper extremity weakness
- stiffness, with poor co-ordination and balance
- spastic, unsteady gait
- painful muscle spasms
- difficulties in arising from chairs and climbing stairs
- foot drop
- stiffness and decreased balance with impact on gait
- head drop
- progressive difficulties in maintaining erect posture, with stooping
- muscle atrophy
- increased lumbar lordosis and tendency for abdominal protuberance
- coughing and choking on liquids (including secretions) and eventually on food
- strained, slow speech
- slurred, nasal, and, at times, dysphonic speech
Other diagnostic factors
- propensity for falls
- sialorrhoea and drooling
- inappropriate bursts of crying or laughing
- cognitive impairment
- features of frontotemporal dementia
- genetic predisposition or family history
- age >40 years
- military service
- professional athletic activity
- cigarette smoking
- agricultural chemical exposure
- lead exposure
1st investigations to order
- clinical diagnosis
Investigations to consider
- electromyography (EMG)
- repetitive nerve stimulation
- MRI brain and spine
- anti-GM1 antibodies
- voltage-gated calcium-channel antibodies
- acetylcholine receptor antibodies
- vitamin B₁₂
- creatine kinase
- lumbar puncture
- HIV test
- genetic testing
Christopher J. McDermott, MBChB, FRCP, PhD
Professor of Translational Neurology and Honorary Consultant Neurologist
University of Sheffield
Faculty of Medicine, Dentistry and Health
Department of Neuroscience
Sheffield Institute for Translational Neuroscience
CJM has received fees for membership of data monitoring committees from Orion Pharma and Orphazyme.
Professor Christopher J. McDermott would like to gratefully acknowledge Dr Laura Simionescu and Dr Jeremy Shefner, previous contributors to this topic.
LS and JS declare that they have no competing interests.
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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