Amyotrophic lateral sclerosis (ALS)

Amyotrophic lateral sclerosis, also known as ALS, is a neurodegenerative disease of the central and peripheral motor nervous system. It is accompanied by increasing destruction of nerve fibers. The disease affects the motor neurons, the spinal cord, the muscles and the musculoskeletal system.

In ALS, both the 1st central motor neuron (in the brain with pyramidal tract to the spinal cord) and the 2nd peripheral motor neuron (in the brain stem and spinal cord with nerves to the muscles) are affected. The disease of the motor nerve cells in the spinal cord and their extensions leads to various symptoms in the innervated muscles (muscle atrophy, muscle twitching, paralysis, etc.). As the disease progresses, there is usually a mixture of flaccid atrophic paresis (2nd motor neuron damaged) and spastic paresis (1st motor neuron damaged).

The disease occurs sporadically and is not contagious, although its exact cause is still unknown. Around 5% of ALS cases are due to a rare hereditary form of the disease, which is inherited in an autosomal dominant or autosomal recessive manner. In this case, ALS also occurs more frequently in families. Two genes (SOD-1 and ALS gene-2) are known to trigger the disease.

There are generally three different forms of ALS:

• Sporadic ALS (around 95% of cases, cause unknown)

• Familial ALS (5 to 10 % of cases)

• Endemic ALS ("Western Pacific ALS" on islands in the Western Pacific)

Differential diagnoses

Related diseases and differential diagnoses of ALS include

• Multiple sclerosis

• syringomyelia

• botulism

• Pseudobulbar palsy

• Multifocal motor neuropathy (MMN)

The disease almost exclusively affects the motor nervous system. At the beginning, ALS often manifests itself with involuntary muscle twitches and muscle spasms. Sensory sensations for hearing, sight, touch, temperature, pain etc. are usually not affected by ALS. In a small number of patients, a slight impairment of mental capacity can be detected. Severe mental impairment, on the other hand, is very rare. Around 15 - 20 % of patients develop frontotemporal dementia with behavioral abnormalities and cognitive impairments during the course of the disease.

Common symptoms of ALS are

• Involuntary muscle twitching (fasciculations)

• Muscle wasting (atrophy)

• Muscle weakness (paresis) in the arms, legs and also the respiratory muscles

• Impairment of the speech, chewing and swallowing muscles

• Spastic paralysis

• fatigue

• Sleep disorders

The diagnosis of ALS should be made by a neurologist. A detailed clinical examination and a sensitive medical history interview are important here.

Things that are checked during the clinical examination:

• Muscle strength

• Muscle wasting (atrophy)

• Muscle twitching (fasciculations)

• Muscle reflexes

• Function of the masticatory, speech and respiratory muscles

An additional examination that can check the function of the peripheral nervous system (PNS) is electromyography (EMG). Here, nerve impulses are examined using a needle. Nerve conduction velocity (NLG) is another way of testing the motor conductivity of the peripheral nerves. Blood, urine and cerebrospinal fluid (CSF) tests can be used to rule out inflammatory diseases that can cause ALS-like symptoms.

Advanced ALS diagnostics include genetic diagnostics and muscle biopsies.

According to the current state of medicine, ALS can neither be cured nor treated causally. The care of ALS sufferers should therefore be multidisciplinary (neurologists, pulmonologists, gastroenterologists, etc.) with specific pharmacological therapy, adapted medical aids and palliative medical treatment. However, a specialized neurologist should remain the main point of contact for those affected and coordinate the therapy. Depending on the dynamics of the disease, a neurological check-up should be carried out at least every 3 to 6 months.

The benzothiazole riluzole prolongs life expectancy by lowering glutamate levels. The resulting increase in liver transaminases can be tolerated up to 5 times the normal value. Summarized data from ALS registers show an extended life expectancy of up to 19 months with riluzole therapy. The usual dosage is 2 x 50 mg per day per os.

Common undesirable side effects of riluzole are

• Nausea

• liver toxicity

• weakness

• fatigue

• rarely neutropenia

Symptomatic and palliative therapy

Symptomatic therapy for ALS is used to alleviate the symptoms of the disease and improve the quality of life of those affected. Many aspects are similar to the principles of palliative therapy.

The goals of palliative ALS therapy include

• Maintaining patient autonomy

• Maintaining quality of life

• Early information after diagnosis is confirmed

• Advice on ventilation and nutrition therapy

• Advice on the possibilities and limitations of pharmacotherapy

• Preparation of a living will

Other therapy modalities for ALS include physiotherapy and occupational therapy as well as therapy for chronic respiratory insufficiency.

Poor prognostic factors are

• Bulbar onset of symptoms (swallowing, chewing and speech muscles)

• Low BMI

Positive prognostic factors include:

• Young age

• Onset as primary lateral sclerosis