Amyotrophic lateral sclerosis, ALS, is a collective name for a group of neurodegenerative diseases that lead to the death of motor neurons in the spinal cord and in the brain.
ALS is characterized by progressive paralysis, that usually starts in a hand, a foot or in the face. The main issue in ALS is that the neurons in the nervous system that control our muscles are degraded. As the signals from the motor neurons to the muscles diminish, the muscles get weaker, start wasting and eventually get paralyzed.
Motor neurons in the brain as well as in the spinal cord can be affected. The upper motor neurons are located in the cerebral cortex. When these cells die the brain has trouble coordinating and relaxing the muscles. This has negative consequences on the fine motor skills of the afflicted person.
The lower motor neurons are located in the brainstem and on the front of the spinal cord, from the neck down to the lumbar region. These nerve cells are directly connected to muscle fibers in different parts of the body, and cause those to contract when one wants to bend an arm, a leg, or a finger, etc. When these nerve cells die the muscles weaken and waste.
In ALS patients, symptoms of loss of both types of motor neurons are almost always observed. Patients thus experience weakness and wasting of some muscles, while stiffness and trouble with coordination in others.
Usually, the disease starts in a single spot, like in a hand or a foot. Over time, the patient experience problems higher up on the arm or leg, and the symptoms spread from the extremities towards the torso. Some time after the first signs, new symptoms usually arise in another extremity on the same body half – if the disease started in the left hand, the left foot may be next. After that the disease usually spreads to the other body half. Sometimes the disease starts in the muscles of the head, leading to problems with speech, chewing, and swallowing of food and beverages.
Regardless of where the symptoms first appear, the disease eventually spreads to the nerve cells that control the respiratory muscles, and when the breathing function is sufficiently impaired, the patient dies from respiratory failure.
Most ALS patients have well preserved cognitive abilities even in the final stages of the disease and are, aside from their paralysis, the same as they have always been. However, in some patients thought and emotional regulation is affected to some extent. An example of this is subtle language changes, like the difficulty to formulate long complicated sentences (this is thus not necessarily a result of the patient easily getting shortness of breath, but because of the trouble to express oneself).
Some patients have trouble regulating their emotions normally, causing them to laugh or cry uncontrollably in unexpected situations. These personality changes, when a person is afflicted, can complicate the interactions between the patient, their relatives, and their assistants since it can be hard to know what is a reaction to the fact that they have an incurable, lethal disease and what is a reaction caused by the disease affecting the brain.
Most patients that are diagnosed with ALS die within three to four years after the first signs appear, however some patients live a lot longer than that. There are long term survivors where, for unknown reasons, the disease progression is very slow. These patients may live for 10 to 20 years with the disease.
Who gets ALS?
Most patients that are diagnosed with ALS are in their sixties and it is somewhat more common for men to be afflicted. ALS is a disease with great variability and unusual cases of ALS have been reported in infants as well as very old (over 90 years of age) patients. The risk of getting ALS at some point in life is about 1 to 400 in an average person. It is known that smoking increases the risk a little, and that the disease is a little more common among farmers and electricians, but the individual risk of getting the disease if you have a risk associated profession is still low.
Known risk factors:
ALS or FTD (frontotemporal dementia) among relatives
Slim body constitution
Weight loss 5 to 7 years before onset of motor symptoms
In the USA, military service has been seen to increase the risk of getting ALS, but no such correlation has been shown for Swedish military service
Protective factors that seem to lower the risk of getting ALS:
Age-related diabetes (type 2)
High coffee intake
High BMI, overweight
Genetic changes that cause ALS:
Approximately 10 to 15 percent of all ALS patients have a hereditary form of ALS. They have a relative with ALS, and the disease is inherited from one generation to the next, so-called familial ALS (F-ALS). Often the disease can be found to be caused by a single mutation in a gene that is passed on in those families.
Genetic studies have identified changes in over 40 genes that are linked to ALS. Mutations in these genes have been found both in patients with F-ALS and in sporadic cases (S-ALS). There are genetic changes that cause ALS, as well as those that can increase or decrease the risk of getting ALS.
The two most frequently occurring changes that are associated with ALS are in the genes C9orf72 and SOD1.
Age-related cellular changes are thought to contribute to ALS
Most people who get ALS (85 to 90 percent) do not have knowledge of any close relatives having had ALS and in these cases the disease is called sporadic ALS (S-ALS).
The cause of the majority of all ALS cases is still unknown. However, the many different hereditary genetic changes associated with ALS, and the studies of the normal function of the proteins those genes encode, have identified a number of cellular changes that may contribute to disease development.
Gene expression and many cellular functions can also change with increasing age, and because of different environmental factors. Having hereditary genetic changes that can cause ALS does not mean that you are born with ALS. The disease usually does not start to develop until 40 to 60 years of age. More than just a genetic change causing faulty proteins is thus needed to develop ALS. It is not until the cell needs to compensate for other age or environmental factors that the accumulation of faulty proteins becomes overwhelming and triggers disease development.
Cellular processes thought to contribute to ALS:
Oxidative stress and overload of free radicals
Impaired degradation and harmful accumulation of faulty proteins
Accumulation of mislocated proteins and RNA
Impaired transport of organelles and molecules in axons
Defective transport of molecules in and out of the cell nucleus
There is one drug routinely used in ALS treatment – Rilutek. It is a tablet taken daily starting immediately after diagnosis. Exactly how Rilutek works has not been established, but it is known to slow disease progression a little, thereby extending the patients life by a few months. The earlier the treatment is started; the more progression is delayed.
There is another drug by the name Edaravone that is approved in some countries, among them the USA and Japan. It seems to slow symptom development a little in some specific patient groups, but unlike Rilutek, Edaravone is an intravenous therapy administered directly into the bloodstream. There are ongoing pharmaceutical studies in Europe intended to determine whether is appropriate to approve Edaravone use in the EU, and whether the procedure to administer the drug can be simplified. In Sweden, The New Therapies Council (NT-rådet) has decided to not approve Edaravone as a treatment for ALS patients until more documentation on the safety, efficacy and cost-effectiveness of the drug has been made available.
Aid and Medical Equipment
During the course of the disease, ALS patients require more and more help from surrounding people to cope with everyday life. However, assistants, speech therapists and occupational therapists can aid in developing new strategies to maintain the patient’s autonomy for as long as possible. When the disease has started seriously affecting the ability to eat and breathe normally, the patient can get help to boost energy and nutrition intake and to breathe more effectively, using a non-invasive ventilation device. Such efforts may seem small but have proven to extend survival better than any drug so far.
In summary, ALS is a disease where specific parts of the nervous system are degenerated, leading to paralysis, great dependence on surrounding people and, eventually, death.