Amyotrophic lateral sclerosis (ALS) is a rare neurological disease that develops due to a loss of motor neurons. These are nerve cells that control voluntary muscle movements such as eating, speaking, and walking. ALS is part of a bigger group of diseases known as motor neuron diseases.
ALS is a progressive disease. This means that the symptoms will gradually worsen over time. Currently, there is no cure for ALS, though there are two FDA-approved drugs that have been shown to improve survival and reduce loss of function.
There are two different categories of ALS: sporadic and familial. Approximately 90 to 95 percent of patients with ALS are thought to be sporadic cases, which means there is no hereditary cause. In approximately five to 10 percent of cases, ALS is genetic or familial, meaning that a patient inherits a disease-causing mutation from one or both of their parents.
Here are some statistics about ALS:
- Most patients develop ALS between the ages of 40 and 70. However, it has been known to develop in younger patients.
- ALS commonly manifests in patients over 60 years of age.
- There are approximately 30,000 people living with the disease in the United States, with 5000 new patients diagnosed every year.
- Estimates suggest that ALS may be the cause of death for approximately five out 100,000 people 20 years of age or older.
- ALS occurs as frequently as multiple sclerosis, and five times more frequently than Huntington’s disease.
ALS: Stages and progression
ALS is a very variable disease from individual to individual. Hence, not all patients experience the same symptoms and the time at which patients develop these symptoms greatly differs. Generally, the progression of ALS can be divided into three stages: early, middle and late stage.
- Early Stage: In the early ALS stage, symptoms generally develop in one particular part of the body. However, mild symptoms can sometimes affect more than one region. The earliest symptoms of ALS involve muscles. Patients generally experience muscle weakness, tightness, cramping and twitching. Patients also experience muscle loss.
- Middle Stage: In the middle stage of ALS, the muscle weakness that was previously limited to one region in the early stage begins to spread to other parts of the body. On the other hand, some muscles continue to be unaffected. Muscle twitching also continues.
- Late Stage: In the late stage of ALS, most voluntary muscles (the muscles a person can control) become paralyzed. At this point, muscle weakness has spread to the mouth, throat and lungs. In fact, the respiratory muscles, which are muscles that help move air in and out, become severely compromised. Patients typically die from respiratory problems at this stage.
The symptoms and course of disease are very variable from individual to individual. Hence, not everyone will experience the same symptoms at the same time.
Some of the earliest symptoms of ALS are:
- Problems with everyday activities such as eating and walking
- Weakness in limbs and hands
- Issues with talking, such as slurred speech
- Muscle cramps and twitching in the limbs, arms, shoulders and tongue
- Issues with balance
- Weight loss
- Reduced muscle tone and mass
- Shortness of breath and problems breathing
- Pseudobulbar effect (uncontrollable periods of laughing or crying)
- Weakness and fatigue
- Muscle stiffness or rigidity
As the disease progresses, these are the symptoms that often develop in patients:
- Muscles become even weaker
- Significant reduction in muscle mass
- Significant difficulties eating (especially chewing and swallowing)
- Significant trouble breathing
- Coughing when eating or drinking
- Reduced food intake
- Difficulty talking and being understood
- Excessive fatigue
- Marked Weight Loss
- Excessive saliva or dry mouth
- Severe headaches and dizziness
- Cognitive and behavioral issues
ALS: Causes and risk factors
As approximately five to 10 percent of ALS patients have familial or genetic ALS, researchers have discovered several genes that are involved in the development of this devastating disease. At this point, studies have identified more than 25 genes that play a role in ALS. These genes are thought to be involved in 70 percent of patients with ALS. Specifically, these are the three most common genes that have contribute to the development of ALS:
The cause of sporadic ALS is not known, however, researchers are hard at work to try and determine what is causing this disease. This is the latest in research regarding the cause of ALS:
- Environmental risk factors: Studies have identified smoking, some occupations such as being in the military, high levels of physical activity, having experienced electric shock, being exposed to chemicals such as heavy metals and pesticides, and having experienced traumatic head injury, as potential risk factors in the development of ALS.
- Inflammation: Inflammation is when a person's immune system attacks normal, healthy cells. Several studies point to neuroinflammation (inflammation of the central nervous system, including the brain) as a major component of ALS.
- Retroviruses: Some researchers have a theory that the presence of retroviruses (a specific type of virus) in the body can predispose an individual to ALS.
- Mitochondrial dysfunction and oxidative stress: Dysfunction of the mitochondria, a major component of every cell, can lead to oxidative stress (a process that takes place due to an increase in free radicals, a type of molecule that is toxic to the body). Studies have implicated a role for oxidative stress in ALS, especially in patients with the SOD1 mutation.
- Glutamate toxicity: Some studies have shown that in ALS, glutamate (a chemical in the nervous system that carries signals between nerve cells) accumulates around a nerve, which causes issues for nerve cell signaling.
- Demographics: sex, age and race are also thought to play a role in ALS.
In order to be diagnosed with ALS, patients must meet the criteria laid out by physicians known as the El Escorial criteria, which include:
- Patient must demonstrate deterioration of lower motor neurons
- Patient must demonstrate deterioration of upper motor neurons
- The disease must be progressive, and spread from one region to another
- There must a lack of signs that indicate other, similar diseases
When a patient presents with typical symptoms of ALS, physicians will conduct a detailed medical and family history and physical examination.
If ALS is suspected, the physician will conduct neurologic tests, which includes tests of muscle and nerve function such as an electromyogram. The physician may also conduct other tests that can help exclude other diagnoses such as MRI, spinal tap, muscle biopsy, blood and urine tests, and nerve conduction study.
Unfortunately, there is no one test that can be done to convey an absolute diagnosis of ALS.
Two medications have been approved for the treatment of ALS: riluzole (Rilutek) and edaravone (Radicava). Riluzole slows down disease progression in a subgroup of ALS patients by reducing levels of glutamate, a chemical in the brain that is present at high levels in ALS patients. Edaravone was found to slow down the decline in daily functioning. However, researchers are not yet sure how exactly edaravone works.
Several treatments can be used to treat symptoms of ALS, rather than the disease itself. Baclofen or diazepam are two drugs that have been shown to help control muscle spasticity. Gabapentin is used for pain treatment, trihexyphenidyl or amitriptyline can help patients swallow saliva, and anti-depressants can help treat depression or anxiety that patients often experience.
Therapies that help manage ALS
Several different types of therapies help patients manage particular aspects of ALS. The major ones are:
- Physical therapy: physical therapists help ALS patients with a variety of issues including managing pain, helping patients walk, helping adjust to a brace and mobility equipment (walker, wheelchair), and practicing low-impact exercises and stretching to to keep as much range of motion as possible.
- Occupational therapy: occupational therapists assist in finding ways to help patients stay independent. They can help find assistive equipment and technology for patients to perform daily activities such as dressing, grooming, eating and bathing.
- Speech therapy: As ALS affects muscles that are involved in speech, communication becomes a major issue in late-stage ALS. Speech therapists help teach patients strategies that can make communication easier, find other, non-verbal modes of communication and provide information on speech-assistive devices.
- Nutritional support: a nutritional support team works with ALS patients, who often have issues eating and swallowing, to ensure that the patient is eating foods that are easy to swallow and meet their nutritional needs.
- Psychological and social support: A support team can help assist patients with financial issues, insurance, and obtaining and paying for equipment. Emotional support, provided by psychologists, is also often necessary for ALS patients and their families
As there is no cure for ALS, patients may turn to alternative and complementary medicine. These are the therapies that patients find can help them with various aspects of ALS:
- Acupuncture: a technique in which a thin needle is inserted into the skin at particular points.
- Chelation therapy: a medical procedure in which a drug known as a chelating agent is given to the patient in order remove toxic heavy metals from the body.
- Aromatherapy: a type of therapy that makes use of oils that are extracted from “aromatic” plants.
- Hypnotherapy: The use of hypnosis techniques with counseling to induce a state of deep relaxation.
- Massage: a type of physical therapy that involves use of pressure on the soft tissues of the body.
- Energy Healing: the channeling of “healing energy” onto a patient to cure them.
- Reflexology: the use of pressure points on particular body parts in order to induce relaxation, and encourage healing.
- Reiki: the use of therapist’s hands at specific positions on or above the body to promote healing.
- Shiatsu: the application of rhythmic pressure at particular places on the body to encourage flow of energy.
Pharmaceutical companies and scientific researchers are conducting studies to find a treatment for ALS. Several advances have been made in preclinical studies and clinical trials. These are some of the future potential treatments that are currently under investigation:
- Antisense oligonucleotides (ASOs): these are drugs that bind to the RNA transcript of a gene (the middle product between gene and protein) that leads to a destruction of the RNA transcript before it ever become a protein. This helps get rid of toxic proteins in patients with familial ALS that have a SOD1 mutation.
- Gene therapy: gene therapy involves the replacement of a defective gene with a normal one.
- Stem cell therapy: injecting stem cells can give rise to a beneficial population of cells that can help protect nerve cells and the brain of patients with ALS.
- Immune system therapies: As inflammation plays a role in ALS, several drugs are being developed that can help regulate the immune system.
- There are other therapies under investigation including BHV-0223 (new formulation of riluzole), GM604 (prolongs motor neuron survival), Arimoclomol (removes toxic SOD1 protein), AT-1501 (binds and blocks CD40 ligand, which is overactive in ALS), VM202 (improves the survival and growth of nerve cells), Reldesemtiv (improves muscle strength), and Mexiletine (treats muscle cramps).
There are several types of complications that arise in patients with ALS:
- Respiratory (breathing) problems: as muscles that are responsible for breathing eventually become paralyzed in ALS, patients often encounter respiratory problems. Breathing strategies, breathing devices and tracheostomy can help manage respiratory complications.
- Eating problems: similarly, patients with ALS often experience eating problems due to a loss of control over muscles that are responsible for swallowing. This can lead to pneumonia, malnutrition and weight loss. Many patients chose a feeding tube to reduce these risks.
- Dementia: ALS patients have a higher risk of developing dementia and dementia-related conditions. There are medicines that can help slow down disease progression of dementia, but there is no cure.
- Speech problems: speech problems develop due to a loss of motor neurons that control muscles that are responsible for speech. Working with a speech therapist can help at the beginning but eventually patients will need communication technologies and assistive devices to be better understood.
- Pressure sores: patients with ALS are at a higher risk of developing pressure or bed sores.
- Pseudobulbar affect: this means patients come down with sudden, uncontrolled laughter or crying.
- Primary bulbar palsy: caused by loss of nerve cells that control bulbar muscles (which are involved in speech, swallowing and chewing).
- Progressive muscle atrophy: this is primarily characterized by muscle weakness and wasting.
- Primary lateral sclerosis: characterized largely by spasticity with no muscle atrophy.
As the course of the disease is variable among individuals, life expectancy for individual can also greatly vary. These are the statistics for the life expectancy in patients with ALS:
- The average life expectancy is between two and five years from the time of diagnosis
- More than 50 percent of patients live longer than 3 years
- 20 percent of patients live for 5 years or more
- 10 percent of patients live for 10 years or more
- Five percent live 20 years or more
ALS in the future
Over the last decade, there have been significant advances in both the understanding why ALS develops as well as the development of new therapeutic approaches. However, while several clinical trials are currently underway, it is important to understand that there is a history of long-standing failure to successfully transfer therapeutic drugs into the clinic. There needs to be a deeper awareness in the research community for the need of drugs that can be clinically useful and relevant, which can only come about with a better understanding of the issues surrounding clinical trial design for ALS. However, there is hope as there is a growing list of validated preclinical drugs under investigation in trials and can finally lead to an effective disease-modifying treatment.
Coping and support
A diagnosis of ALS can be devastating. There are strategies that can be employed by patients, their families and caregivers that can make the process a little easier:
- Allow yourself to go through all the emotions. It is okay to take time to grieve for yourself or your loved one.
- Talk to family and friends. By reaching out to people that are closest to you, it can help yourself and others better handle the diagnosis.
- Get educated about ALS. The more you know about ALS, the more in control you will feel when dealing the symptoms and consequence of the disease.
- Pick your physician carefully and work with them to determine the best course of treatment for you. Be actively involved in treatment decisions as that can help you feel in charge.
- Fulfill lifelong dreams.
- Make important decisions early on. It is best to make major decisions before the disease progresses so you have more time to pick between options.
- Join a clinical trial.
- Embrace technology. Technology is very useful as it can help you be more mobile and communicate with people around you.
- Be comfortable asking for help.
- Remain hopeful and positive.