Amyotrophic Lateral Sclerosis – historical background  

Jean Martin Charcot, a french neurologist, was the first who comprehensively described the Amyotrophic Lateral Sclerosis with its major symptoms in 1873. According to this in Europe the disease sometimes is called Morbus Charcot. In America it often is called Lou Gehrig´s disease, named after an American baseball player, who fell ill with Amyotrophic Lateral Sclerosis in the thirties.

Amyotrophic Lateral Sclerosis – occurrence and frequency  

Amyotrophic Lateral Sclerosis is one of the most common progressive disorders of the motor system. Annualy 0.6 to 2.4 per 100,000 population become ill with this disease. In the northern regions of Europe Amyotrophic Lateral Sclerosis seems to appear a bit more frequently. In fact 3 to 8 persons of 100,000 inhabitants suffer from this disease. In Germany about 6000 people are affected. The frequency increases with age. The median onset is between 50 to 70 years of age.

Amyotrophic Lateral Sclerosis – symptoms  

Amyotrophic Lateral Sclerosis is a progressive degenerative disease of the motor system. It affects two different groups of nerve cells: upper and lower motor neurons. The task of these neurons is voluntary movement. Upper motor neurons are located in the brain. Their fibres (axons) connect the brain with brain stem and spinal cord, where the impulses are transmitted to the lower motor neurons. The axons of the lower motor neurons lead to muscle fibres, which are innervated (stimulated) by them. A figure illustrates these anatomic structures in  www.muskelkrankheit.de. One nerve fibre innervates a certain number of muscle fibres, from 6 in very small muscles to 1000 in large muscles. Nerve fibre and innervated muscle fibres together are called motor unit.

Degeneration and disturbance of function of the lower motor neuron leads to paresis (weakness). Following wasting of muscles occurs. The wasting is called atrophy. The syllable “myo” means „muscle“, so  „amyotrophic“ explains the wasting of muscles. In the course of the disease strength and stamina ot the muscles are declining.

At the same time of degeneration of nerve cells and fibres the body starts to repair. Maintained nerve fibres are sprouting in muscle tissue and build new connections to muscle fibres, where the according nerves are degenerated. So the motor unit (see above) gets bigger.

The degeneration of the upper motor neuron leads to weakness, as well. Stiffness of muscles, so-called spasticity can occur by the dysfunction of this group of cells. Dexterity may detoriate.

For Amyotrophic Lateral Sclerosis being a disorder of upper and lower motor neuron the primary symptoms depend on which group of nerve cells is more affected. In most cases the symptoms of the lower motor neurons dominate.

Amyotrophic Lateral Sclerosis often starts with weakness, mostly beginning in forearms and hands (40 – 50%), less often in legs (25 – 30%), here mostly with a weakness of the foot elevators. Usually the symptoms start unilateral. About 25 % of patients present with disturbances of muscles of the throat leading to difficulties in speaking and swallowing. Weakness is slowly spreading over the body and may involve arms and legs as well as trunk.

Further typical signs are so-called fasciculations. These are involuntary twitches in muscles without pain due to contractions of muscle fibres belonging to one motor unit. Nearly every patient presents with fasciculations. Yet the sign is not specific for this disease, it can  occur even in healthy persons as well.

Patients often complain about cramps of different muscle groups.

Difficulties in speaking (dysarthria) and swallowing (dysphagia) may occur in the course of the disease. Dysphagia usually affects more liquids than solids. Drooling (sialorrhoe) is not caused by an overproduction of saliva but is due to severe dysphagia.

Sometimes inappropriate spontaneous laughing or crying may appear. It is an effect of brain stem dysfunction.

In late stages muscles of respiration are involved. First symptoms may be sleep disturbances, nightmares, frequent waking, morning headache and daytime sleepiness as well as shortness of breath on exertion. Patients are often frightened they may suffocate. But in the last stage of the disease they get narcotised by CO2 accumulation in blood resulting in loosing consciousness without the feeling of suffocation. In the last fifteen years increasing knowledge in therapy of this condition was gained. 

Amyotrophic Lateral Sclerosis – diagnosis  

Diagnosis of Amyotrophic Lateral Sclerosis is made regarding patient history, clinical examination and additional investigations. Especially measuring of nerve conduction velocity, electromyography and magnetic resonance imaging (MRI) of spine and sometimes brain as well as laboratory testing are to be done. 

In 1990 experts of the World Federation of Neurology (WFN) met in Spain to find a consensus of diagnostic criteria which were revised in 1998. They are called „El Escorial criteria“ (http://www.wfnals.org/guidelines/1998elescorial/elescorial1998criteria.htm)

According to these criteria diagnosis of Amyotrophic Lateral Sclerosis requires

Presence of

A 1: evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination,

A 2: evidence of upper motor neuron (UMN) degeneration by clinical examination,  

A 3: progressive spread of symptoms or signs within a region or to other regions,

as determined by history or examination,

and absence of 

B 1: electrophysiological and pathological evidence of other disease processes that might explain the signs of LMN and/or UMN degeneration  

B 2: neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiological signs.

Amyotrophic Lateral Sclerosis – etiology (cause)  

Amyotrophic Lateral Sclerosis, sporadic form

More than 90% of patients with Amyotrophic Lateral Sclerosis suffer from the sporadic form. That means there are no further members of their family concerned.

The etiology of the disease is still unknown, but there are a couple of theories. A disturbance of the immune system has been discussed for years but appears to be unlikely. Trials with various immunomodulatory treatments failed. Also there are no convincing clues to a viral disease.

On the other hand disturbances of the metabolism of glutamate, an excitatory neurotransmitter, may lead to an injury of motor nerve cells. The role of metal toxicity is uncertain. Treatment with chelating (detoxifying) agents did not show any benefit.

Further theories include

Ø      Dysfunction of filaments of nerve structures

Ø      Depletion of neurotrophins 

Ø      Dysfunction of mitochondria (mitochondria = power station of the cell)

Ø      Hormonal alterations

Ø      Altered DNA repair (DNA = genetic information).

None of these theories has been leading to a therapy up to now.  

Familial Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis is inherited in less than 10% of the patients. In the majority it is inherited in an autosomal dominant fashion. That means, that the next generation has a risk of 50% to fall ill with this disease. The familial variant should be suspected when familiy members of successive generations are definitely affected by the disease. In up to 20% of the familial variant a mutation on chromsome 21 has been demonstrated. The gene ist called Cu/Zn SOD 1. Although the gene and the product are known there is no specific therapy available, but it bears the possibility to support genetic consulting.

Amyotrophic Lateral Sclerosis – Therapy  

Amyotrophic Lateral Sclerosis can not be healed, but patients with Amyotrophic Lateral Sclerosis can be treated, and they have to be treated.

Detailed information on therapy can be received by our Internet-Site:

www.als amyotrophic-lateral-sclerosis.com/therapy

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