Amyotrophic lateral sclerosis (ALS)

Essentials

  • The terms ALS and motor neurone disease (MND) are often used interchangeably. ALS is the most common form of MND.
  • ALS is a progressive neurodegenerative disorder involving motor neurones in the brain and spinal cord, which leads to progressive weakness and atrophy of the voluntary muscles without sensory deficit.
  • The functions of the autonomic nervous system and the sphincters remain intact.
  • Mild cognitive impairment is found in 40% of the patients.

Aetiology

  • The aetiology of ALS remains unknown.
  • The disease is not contagious.
  • In Finland, approximately 20% of the patients have the disease in the family. The term familial amyotrophic lateral sclerosis (FALS) is used in these cases. This condition, however, does not have a generally adopted definition. If one of the family members has a verified mutation that causes the disease, the term is justified. In an isolated case of ALS, the risk of the descendants or siblings falling ill with the disease is in a class of one percent only.
  • The dominantly inherited C9ORF72 mutation is the most common one. This mutation also causes frontotemporal lobar degeneration (FTLD) (Frontotemporal lobar degeneration). The demonstration of the mutation for diagnostic purposes is reasonable in exceptional cases only.
  • The demonstration of the recessively inherited D90A/SOD1 mutation is meaningful considering the prognosis and the genetic counselling.

Epidemiology

  • Incidence: 1–2.5/100,000
  • Prevalence: 2.5–8.5/100,000 (higher prevalence in certain areas of the Western Pacific)
  • Median age of onset 55 years

Symptoms

  • The most common primary symptom is distal weakness of the upper or lower extremity in functions requiring normal muscle strength.
  • Leg cramps are typical.
  • In bulbar involvement, the initial symptom is deterioration of speech and swallowing. Atrophy and fasciculations of the tongue may be seen. Inability to push out the tongue and difficulty in forming the sound ’r’ (in languages where ’r’ is pronounced with alveolar trill) are typical first symptoms.
  • 10–25% of patients may complain of mostly slight distal numbness, paraesthesiae or mild pain.

Clinical course

  • Muscle weakness and atrophy progress proximally starting in the distal parts and spread to other limbs, respiratory muscles and to the bulbar area. The weakness can also begin in the bulbar area and progress distally.
  • Upper motor neurone involvement leads to spasticity (not always detected) and to accelerated tendon reflexes. Babinski's sign is positive in about 50%.
  • Lower motor neurone damage weakens muscle tonus and reflexes, which is why the tonus can vary between individuals.
  • When upper motor neurone damage is dominant, the term primary lateral sclerosis (PLS) is used.
  • As the disease progresses, muscle atrophy and poor muscle tone become dominant.
  • The cardiac muscle is not involved.
  • Ocular muscle functions are spared until the final stage of the disease.

Findings

  • Atrophy of the small thenar and palmar muscles is the most prominent finding.
  • Weight loss is mainly result of muscular atrophy.
  • Fasciculations mainly in the muscles of the limbs and in the tongue. Fasciculations alone are not a sign of a pathological situation.
  • True and persistent sensory symptoms should prompt a search for an alternative diagnosis.
  • Subtle frontal type dementia may be the first sign.

Investigations

  • There are no specific findings in laboratory tests. Plasma CK and CSF protein concentrations may be slightly increased.
  • ENMG (electromyography and nerve conduction studies), usually requested by a neurologist
    • Fasciculations, polyphasia
    • Fibrillations in the denervated muscles
    • Normal motor nerve conduction velocity
    • Changes also in symptomless muscles
    • A control ENMG is often required.
  • CT or MRI imaging of the head and neck is recommended to exclude other CNS disorders, cervical spondylotic myelopathy and neoplasm.

Prognosis

  • Refrain from predicting survival time.
    • Median survival is about 3.5 years from onset of symptoms, but 10% may live over 10 years.
    • Older age at onset, and bulbar and/or respiratory dysfunction early in the clinical course indicate poorer prognosis.
    • The basic cause of death is ALS, but in most cases the immediate cause is pneumonia.

Treatment

  • Therapy is symptomatic.
  • Riluzole (50 mg × 2) has been shown to prolong survival or postpone the start of mechanical ventilation, but only by a mean of 3 months [Evidence Level: B]. It does not affect the clinical symptoms.
    • Paradoxically, it may cause muscle weakness but this will subside to the natural level when the drug is discontinued. Also nausea may occur.
    • Basic blood count and plasma ALT concentration should be determined before and during riluzole therapy. Treatment should be discontinued if ALT levels increase to five times the upper limit of normal.
    • Treatment is initiated by a specialist in motor neurone diseases.

Asthenia

  • Physiotherapy aims at maintaining muscle condition and mobility. The exercises must be adjusted to the patient's performance. The muscles cannot be made stronger by training. Contractures are prevented.
  • Occupational therapist should help with the acquisition of supports and assistive devices.

Cramps and spasticity

Salivation and mucus production

  • Scopolamine patches placed at the submandibular angle
  • Amitriptyline 25–50 mg × 2–3 p.o. (the drug of choice)
  • ALS patients rarely benefit from antitussives.
  • Postural therapy and drainage
  • Glycopyrronium 0.1–0.2 mg s.c. if the other therapies fail
  • Portable suction device for use at home (use needs to be instructed).
  • Botulinum toxin injected into the submandibular and parotic glands under ultrasound guidance. Keep in mind that the doses are product-specific.

Difficulty with speech

  • Early referral to a speech therapist for acquisition of swallowing and communication aids.
  • Paroxysmal involuntary crying and laughter are caused by pseudobulbar paresis. Imipramine derivatives may help.
  • Speech difficulties may partly be caused by frontotemporal dementia.

Dysphagia

  • Semi-solid food
  • Instructions given by a speech therapist
  • Nasogastric tube (NG) feeding only temporarily
  • Percutaneous endoscopic gastrostomy (PEG) [Evidence Level: C]
  • The carers should be taught the Heimlich manoeuvre (picture (Heimlich maneuver)).

Ventilatory failure

  • Elevations for the bed
  • Oxygen nasal cannulas
  • Nasal BiPAP (Bilevel Positive Airway Pressure) [Evidence Level: B] or other therapy (for use at home)
  • Assisted ventilation with tracheostomy is considered only after serious discussion of the implications with the family, and the neurological and respiratory care team. Respirator therapy should not be recommended as a primary option. The decisions made together with the patient about the eventual use of respirator therapy are recorded in the medical chart and acute care teams are informed of the decision. Drawing up of a written living will is advisable.
  • In the terminal phase, methods of palliative care

Evidence Summaries


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