What is amyotrophic lateral sclerosis (ALS)?

Amyotrophic lateral sclerosis (ALS) is a disease in which the muscles in the limbs, throat and tongue, as well as those needed for breathing, gradually become weaker and weaker. However, it is not a disease of the muscles themselves, but only the nerves that move the muscles and control movement (motor neurons) are affected. As a result, the brain no longer gives the command to move the limbs, resulting in weakness and muscle thinning. On the other hand, the body's senses, vision, hearing and internal organ functions are usually preserved.

How many patients have this disease?

The number of new cases of the disease per year is approximately 1-2.5 per 100,000 people. Nationally, according to the number of recipients of medical care for specific diseases in 2014, approximately 9,950 people suffer from this disease, and the number is gradually increasing.

Are there any gender, age and occupational differences in terms of prevalence of ALS?

The disease is 1.2-1.3 times more common in men than in women, and is slightly more common in men. The disease can affect people of any age from middle age onwards, but people in their 60s and 70s are most susceptible. Rarely, it can also occur in younger generations. It is not common in people in any particular occupation.

What causes this disease?

The cause of the disease is not yet fully understood, but various theories have been put forward, including a link with ageing nerves, abnormal metabolism of excitatory amino acids, oxidative stress, impaired protein breakdown, or abnormal mitochondrial function. As described in the next section, more than 20 causative gene alterations have been found in familial ALS. In Japanese familial ALS, the gene superoxide dismutase (SOD1) is the most common cause (approximately 20%) and may be associated with other genes such as FUS, TARDBP, VCP and OPTN. On the other hand, familial ALS in Europe and the USA is most often caused by the gene C9ORF72, and differences by race and country have been noted.

Is the disease inherited?

In most cases (about 95%) the disease is not inherited. Unless you have a blood relative with the same disease, such as one of your parents, an uncle, aunt or grandparent, you do not need to worry about inheritance. On the other hand, about 5% of all cases of ALS run in families, and are known as familial ALS. In this case, one of the parents, a sibling or a grandparent has the same disease. In about 20% of cases, the cause is found in the superoxide dismutase (SOD1) gene mentioned above.

What are the symptoms of this disease?

In most cases, the disease begins with difficulty using the fingers and muscles from the elbow upwards become weak and emaciated. It may also begin with difficulty speaking or swallowing food, or weakness of the muscles in the legs due to thinning. Wherever the symptoms start, eventually all the muscles in the body, including the muscles for breathing, become weak and it becomes difficult to move around. Loss of strength in the throat muscles makes it difficult to pronounce (dysarthria) and to swallow water or food (dysphagia). Saliva (drool) and phlegm (phlegm) may also increase. Weakening of the respiratory muscles makes it difficult to breathe adequately. Even in advanced stages of the disease, there are usually no problems with sight, hearing or body sensation, and the muscles that move the eyes and eyelids, as well as those needed for urination and defecation, are known to show fewer symptoms. On the other hand, cognitive symptoms, mainly language (speech) and behavioural symptoms, may be present, although forgetfulness is less noticeable.

What is the course of the disease?

The disease is always progressive and the symptoms do not lessen once the person has the disease. It can start in any part of the body and eventually affect all the muscles in the body, eventually the breathing muscles (respiratory muscles) also stop working and the majority of people suffer from respiratory failure. Without a ventilator, the time from illness to death is approximately two to five years. In some cases, the disease progresses slowly over a decade or more without the use of a ventilator, while in others, respiratory failure occurs quickly, in as little as one year. The progression of the disease has been shown to be particularly rapid in older patients, those with symptoms of difficulty speaking or swallowing, those who develop the disease from their breathing muscles, and those who lose a lot of weight or weaken their neck muscles at an early stage of the disease. As such, there are significant individual differences in how ALS develops and progresses, so it is necessary to respond flexibly to each individual patient.

Has research into treatments been conducted?

Various studies are being conducted worldwide on treatments for ALS, including research into gene therapy and regenerative medicine. In recent years, research into the development of therapies using induced pluripotent stem cells (iPS cells) has been very active. In this context, several oral and injectable drugs are being developed. The latest clinical trials can be found at https://rctportal.niph.go.jp/en, the clinical research information search website of the National Institute of Health Sciences.
Enter the keywords 'ALS' or 'amyotrophic lateral sclerosis' to search.

What about nutrition when you can no longer eat?

Liquid food can be fed through a tube through the nose to the stomach or through a simple endoscopic procedure in which a tube is passed over the skin of the abdomen into the stomach (gastric banding) and liquid food is fed directly into the stomach. Currently, the most common method of nutritional support is through a 'gastric tube'. Intravenous drips are also administered as required.

Is rehabilitation effective?

If muscles are not used at all, they will lose weight and weaken by themselves, and joint contractures will occur accordingly. Rehabilitation with moderate exercise and joint movement can help. However, excessive exercise should be avoided as it may strain the remaining motor nerve cells.


The treatment of ALS.

Symptomatic treatment (methods to alleviate various symptoms).

  • Muscle and joint pain
    Daily rehabilitation is very important for muscle and joint pain associated with ALS. For information on how to carry out rehabilitation, please consult your doctor, local public health nurses, care managers of long-term care insurance or specialists of the Intractable Disease Medical Liaison Council in each prefecture (Intractable Disease Medical Liaison Council, Base Hospital for Intractable Disease Treatment, etc.). Note that the HAL medical lower limb type was approved as a medical device in 2015 based on the results of clinical trials in this disease (https://doi.org/10.1186/s13023-021-01928-9) and has been covered by insurance as a walking exercise treatment (by robot suit) since 2016 .
  • Insomnia.
    Sleeping pills and stabilisers are used for insomnia caused by lack of physical freedom and anxiety about the illness.
  • Dyspnoea.
    Dyspnoea can be treated by non-invasive breathing support using a nasal mask or by invasive breathing support using a tracheostomy. Generally, when a tracheostomy is necessary, regular suctioning of sputum (phlegm) is required, and consultation with a health care professional is necessary on how to do this.
    Even if a ventilator is used, the patient basically remains at home. Electricity is essential for the ventilator and aspirator, so it is necessary to prepare for power outage in the event of disasters such as earthquakes and typhoons.
  • Difficulty in swallowing
    If there is difficulty swallowing, it is useful to pay attention to feeding and swallowing techniques, such as devising food forms (as a rule, soft, moist, light-tasting and cold foods are easier to swallow), swallowing small amounts in the mouth and pulling back the chin, as described below. If the difficulty in swallowing progresses further, there are other options, such as a tube through the skin of the stomach into the stomach (gastroduodenal tube), a tube through the nose into the stomach via the oesophagus to supply a liquid diet, or intravenous nutritional support. Currently, gastric tube (also called PEG, https://www.bostonscientific.com/jp-JP/health-conditions/peg/peg-01.html) is the most common method of nutritional support. The creation of a gastric tube after the patient's respiratory function has deteriorated is more dangerous, so please discuss this with your doctor as soon as possible.
  • Communication.
    Communication with family members and others becomes more difficult as symptoms such as difficulty in speaking and hand-movement progress. It is important to learn new means of communication as soon as possible. Practice is required before a communication board called a letter board can be used (see the introduction to letter boards on the website of the Niigata Branch of the Japan ALS Association: http://www.jalsa-niigata.com/). If the patient still has some body and eye movement, communication is possible by selecting the appropriate computer multimedia (communication device) and input switches. Consult your doctor, local public health nurses, care managers of long-term care insurance or specialists of the Medical Liaison Council for Intractable Diseases in each prefecture (consult with the Medical Liaison Council for Intractable Diseases, Base Hospitals for Intractable Disease Care, etc.).

What is needed for the development of future therapies.

In Japan, there are few data on the natural history of ALS patients, which is a very important issue for designing effective clinical studies and trials with a limited number of patients. To solve this problem, a nationwide survey of ALS patients called JaCALS has been initiated by the Ministry of Health, Labour and Welfare's "Research on Neurodegenerative Diseases" group (principal investigator: Dr Imaharu Nakano, Director of Tokyo Metropolitan Neurological Hospital) ( http://www.jacals.jp The central secretariat is the Department of Neurology, Nagoya University). Currently, JaCALS is conducting a large-scale research study combining various clinical and genetic information, which has not been done much in ALS research worldwide until now. As of January 2015, the number of registered ALS patients has reached 1,041, exceeding 1,000. All ALS patients who have been diagnosed and informed of their condition are eligible for this project, and those who agree with the JaCALS philosophy are encouraged to participate.



Diet and nutrition in amyotrophic lateral sclerosis (ALS)

We need to get enough carbohydrates, fats, proteins, vitamins and fluids every day, and ALS patients are often deficient in these nutrients and fluids due to the following factors. First, the ability to swallow itself becomes impaired (called dysphagia). This makes eating time-consuming and tiring, and the food may enter the trachea and suffer from choking (known as aspiration). This makes eating less enjoyable and, in turn, the patient becomes reluctant to eat, resulting in not getting enough food and fluids. Secondly, the patient's hands and arms become weak and tired, so they are unable to carry sufficient amounts of food and liquids to the mouth. Thirdly, as limb weakness increases and people need assistance with toileting, they tend to consciously reduce the amount of water they drink in an attempt to reduce the frequency of toileting.

This section discusses measures to combat dysphagia, the most common cause of undernutrition and fluid deficiency. The goal is to get enough calories, nutrients and fluids and to prevent aspiration. Nutrition is achieved by eating high-calorie, high-protein foods so that small amounts of nutritional requirements are met. Care should also be taken to ensure that vitamins and minerals are taken at the same time.

There are two ways to prevent aspiration: by eating in a different way and by using different food forms.

(1) Dietary practices.

It is advisable to sit up as much as possible when eating and to remain in this position for about an hour after finishing a meal. It is important to take less food and liquids in the mouth at one time, alternating between solid foods and liquids. Swallowing with the chin pulled back reduces choking. If you cannot sit up, you can raise your upper body 30-40 degrees on your back and place a pillow under your head so that your head is slightly elevated. When swallowing, it is important to concentrate on swallowing, saying 'Come on, let's swallow'. Swallowing while watching TV or talking can make it easier to choke. Increasing the number of times you eat and reducing the amount of food you eat at one time is also a good idea. If you have breathing difficulties, it can be difficult to breathe when your stomach is full of food, so eating more often can help to reduce the difficulty of breathing.

(2) Food forms.

The best foods are soft, moist and smooth with no mash. Meat and fruit should be pureed and softened. Bread should be soaked in milk or other suitable drink before eating. Canned foods are good foods because they are soft and moist. Thickened liquids are easier to swallow than plain liquids, so it is good practice to thicken soups, for example by adding grated potatoes. Thickening agents (ingredients that thicken the liquid) are available at pharmacies. Liquids are difficult to drink when hot, so it is advisable to cool them down.

The information on this page is based on content from the following websites Reference source: Homepage of the Information Centre for Intractable Diseases (as of September 2022).