What is Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))?
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a condition where the nerves controlling muscle movement progressively break down. It’s the most common disease of its kind, and can occur ‘out of the blue’ or run in families. In the past, it was distinguished from other similar nerve diseases based on where the first symptoms appeared in the patient. However, it’s now known that ALS can show up in many different ways.
The causes of ALS are still not well understood. There are various theories involving possible genetic changes or unknown factors that could suddenly trigger the disease. Most often, the disease first shows signs in the arm muscles but can also start affecting speech or other body parts. Over time, ALS can potentially lead to difficulty in breathing due to muscle weakness, and unfortunately, death.
At this time, there is no cure for ALS. Yet, several treatments are available that can help to manage its symptoms and improve the quality of life for those affected.
What Causes Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))?
The exact cause of ALS, or Amyotrophic Lateral Sclerosis, is still unknown. However, several factors may play a role in its development. These can include genetic mutations, damage from harmful substances in the body, imbalance in neurotransmitters, problems with cell energy production and protein breaking down, altered brain signals, issues in nerve transport, and inflammation in the nervous system.
Some risks may increase the chances of getting ALS, like playing certain sports, being in the military, smoking, exposure to heavy metals, pesticides, toxins from bacteria, and magnetic fields. It seems that ALS comes about from a combination of our genes and the environment we live in.
Scientists have found over 120 genes that might be connected to ALS – abnormal proteins from these faulty genes might play a role in causing this disease. For instance, genes known as TDP-43 and FUS, involved in our RNA functioning, could play a significant role. People with abnormal forms of these genes often have misplaced proteins that lead to nerve cell damage.
Another gene, C9ORF72, has been linked commonly with ALS. This gene particularly involves in cell membrane transportation and autophagy — a process that removes unnecessary or faulty components. When this gene is mutated, it can lead to both ALS and another condition called frontotemporal dementia (FTD). Some people with this gene mutation might develop ALS, some might develop FTD, while others might have both conditions. Generally, by age 60, about half of the people with this gene mutation develop ALS, and almost all do by age 80.
Lastly, a gene called Superoxide dismutase 1 (SOD1), was the first one connected to ALS back in 1993. SOD1 is responsible for transforming harmful superoxide radicals into less harmful molecules. When this gene is faulty, it can cause an imbalance in protein creation, leading to ALS. This type of ALS is found in about 20% of inherited cases and 1% of non-inherited cases. Other factors like changes in the structure and function of cells and disruption in muscle-nerve connections may also contribute to ALS. For instance, these disruptions are usually seen a few weeks before muscle symptoms begin. Animal studies often use the abnormal forms of SOD1 and another gene, profilin 1 (PFN1), to study ALS further.
The potential involvement of the brain-gut-microbiota — the connection between our brain, gut and its bacteria — in causing ALS, was also suggested.
Risk Factors and Frequency for Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
Amyotrophic lateral sclerosis, commonly known as ALS, comes in two forms. The majority, around 90% to 95%, are random cases, known as sporadic ALS, which are more common in men. The rest are inherited from family members, known as familial ALS, and affect men and women equally.
Most patients with sporadic ALS have a genetic predisposition for the disease, while others develop it due to environmental factors. Men’s lifetime risk of getting ALS is 1 in 350, while for women, it’s 1 in 400. The disease typically begins around 64 years of age and the risk is highest at around 75 years old. In 2020, there were over 120,000 ALS cases in Europe and 800,000 in the United States. 380,000 cases are expected worldwide by 2040.
- ALS affects 1 to 2.6 out of every 100,000 people.
- Between 4 and 5 out of 100,000 people have the disease at any given time.
- The rate of new cases each year ranges from 0.26 per 100,000 people in Ecuador to 23.46 per 100,000 in Japan.
- The number of people with the disease at a given point ranges from 1.57 per 100,000 in Iran to 11.8 per 100,000 in the United States.
Signs and Symptoms of Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
Amyotrophic lateral sclerosis, or ALS, can show itself in many ways. The key indicator of this condition is the presence of symptoms related to both “upper” and “lower” motor neurons, which are special nerve cells that control muscle movement. Symptoms of “upper” motor neurons (UMN) include overactive reflexes, difficulty with fine movements, clumsiness, and muscle stiffness. Problems with speech and swallowing are common UMN symptoms. “Lower” motor neuron (LMN) symptoms include muscle wasting and twitching. Regardless of whether symptoms are classified as UMN or LMN, weakness is a standout feature of ALS.
The initial symptoms of ALS often signal how the condition will progress and can provide some insights into the patient’s prognosis. Most patients initially show uneven symptoms related to LMN, specifically in the arm or leg. Early signs can include hand and shoulder muscle weakness and difficulty lifting the foot (foot drop). About a quarter of ALS patients first show symptoms related to the muscles used for speaking and swallowing, aka the bulbar muscles, including speech difficulties, swallowing difficulties, overly nasal speech, muscle spasms in the larynx, inadvertent cheek or tongue biting, and excessive saliva production. Muscles related to the eyes and evacuation remain unaffected until the later stages of the disease. In some cases, patients initially show weakness in the respiratory muscles or general weakness along with bulbar muscle-related symptoms.
- Overactive reflexes
- Difficulty with fine movements
- Clumsiness
- Muscle stiffness
- Difficulty speaking or swallowing
- Muscle wasting
- Muscle twitching
- Weakness
About 30-50% of ALS patients are found to struggle with thinking and memory. Among them, 15-20% are diagnosed with a specific type of dementia known as frontotemporal dementia or Pick’s disease. In addition to visible dementia, patients may experience issues with high-level thinking skills and speech fluency, along with behavior changes like a lack of motivation and inappropriate behavior. Excessive crying, laughter, or yawning (known as pseudobulbar palsy, caused by damage to specific motor neurons), along with symptoms of the autonomic nervous system (like constipation), unusual sensations, and pain (due to lack of movement and muscle cramps) can also occur.
ALS is considered part of a spectrum of motor neuron diseases, which include progressive muscular atrophy and primary lateral sclerosis as well. Some experts believe that progressive muscular atrophy might be a form of ALS that primarily affects the LMN, but eventually shows signs of affecting the UMN as well. Similarly, primary lateral sclerosis primarily affects the UMN initially but later impacts the LMN too. These issues define the specific form of the disease.
ALS can present in a variety of ways, named as traditional ALS clinical phenotypes, and affect different body parts initially. These include typical spinal onset, bulbar onset, and several others.
ALS generally progresses in a predictable pattern and does not have periods of remission or sudden worsening. While the rate of progression can differ between individuals, the pattern of symptoms generally starts with unilateral limb weakness, which spreads to include the other limb on the same side, and then to the limbs on the other side of the body, and finally affects the bulbar muscles.
Testing for Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
Diagnosing ALS (Amyotrophic Lateral Sclerosis) can be a challenge due to symptoms that vary between individuals, normal test results, and traits that it shares with other nerve disorders. Doctors often rely on certain criteria, known as the El Escorial and Awaji standards, which were developed to guide diagnosis and patient participation in clinical trials. According to these standards, to diagnose ALS, there must be evidence (from clinical exams, electrical tests, or tissue analysis) of the combined degeneration of upper and lower motor neurons. The disease should also progress over time and not resemble any treatable conditions.
Patients suspected of having a motor neuron disease should have nerve conduction studies and electromyography (EMG), which can support the diagnosis in most cases, especially when symptoms are unclear. The EMG can show acute denervation (nervous tissue damage), chronic denervation (nerve damage over time), and chronic reinnervation (nerve tissue regrowth). Normally, sensory signals are unaffected, but the strength of the motor nerve signals may decrease before weakness is evident. To diagnose ALS using EMG, there must be acute or chronic denervation in at least three parts of the spine or in three extremities, including muscles that are controlled by diverse nerve roots. There should be no features of a disease called demyelination, which attacks the insulating layer around nerve fibers.
Radiology, particularly MRI, is mainly used in diagnosing ALS to rule out other potential causes of the patient’s symptoms. Generally, MRI results will be normal in patients with ALS. However, sometimes there can be certain signs indicating ALS, such as decreased signal strength within the motor cortex, lesions with increased signal visibility, or the “motor band sign,” which is due to an accumulation of iron in the precentral gyrus. Some special techniques of MRI, such as spectroscopy and diffusion tensor imaging (DTI), can also reveal signs of upper motor neuron disease.
The King’s staging system is used to track the progression of ALS. This system includes various stages: from symptom onset to needing noninvasive ventilation and eventually death. Most patients receive a diagnosis in stage 2. Tools like ‘thinkALS’ and ‘MND Red Flag’ can aid in earlier diagnosis. In the light of new gene-specific treatments in clinical trials, upon diagnosis, genetic testing is recommended, particularly for the SOD1 and C9ORF72 genotypes. This screening can be useful for patients with a family history of dominantly inherited diseases, giving insights on disease progression and genetic risk factors.
Treatment Options for Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
Amyotrophic Lateral Sclerosis (ALS) treatment involves a range of disciplines like physical, occupational, and speech therapies. It also includes home-based ventilation therapy, dietary support, counseling, caregiver training, cognitive checks, and end-of-life care. The primary focus of treatment is managing the symptoms.
There are only a few medications approved for ALS treatment, and their primary effect is to help extend the patient’s life. These include Riluzole, Edaravone, and Sodium Phenylbutyrate. Riluzole is commonly recommended for ALS patients as it reduces glutamate-induced toxicity. This drug has been found to increase survival rates and slow down symptom progression, particularly in patients who were symptomatic for less than 5 years, and do not require a tracheostomy.
Edaravone helps reduce oxidative stress by scavenging harmful free radicals and slows down the rate at which the disease progresses. This treatment tends to benefit patients who are in the early stages of ALS, living independently, and have a high respiratory capacity. However, caution is required when using it in patients with asthma.
Sodium Phenylbutyrate helps reduce the stress response in cells, and when combined with Taurursodiol, it can slow down neuronal damage and the decline in function.
As ALS weakens the respiratory muscles, patients will often need regular checks and discussions about respiratory management and future options like tracheostomy, chronic breathing support, and noninvasive ventilation. When respiratory capacity decreases significantly, patients can benefit from noninvasive ventilation. When this is no longer effective, invasive ventilation may be considered.
ALS also affects the muscles used for chewing and swallowing leading to difficulty in eating and subsequent weight loss. Therefore, emphasis is put on consuming calorie-rich foods and supplements. If significant weight loss or swallowing difficulties are detected, then feeding through a tube may become necessary.
As the disease progresses, patients will have difficulty speaking, and speech therapy will only provide limited benefit. Thus, alternative methods for communication may become essential. With the decrease in mobility, patients will often require aids like canes, crutches, and eventually wheelchairs. Patients also often struggle with frequent and painful muscle spasms which are treated with medications.
It’s also common for patients with ALS to suffer from depression, and treatment will typically help to improve their quality of life. Patients may also experience a range of other symptoms which can be treated with different medications and therapies.
Patients should also be made aware of their end-of-life care options and given help in managing dyspnea (shortness of breath) and anxiety. Helping patients get a good night’s sleep by treating any underlying issues is also recommended.
Research is ongoing into potential future treatments for ALS, including the use of nanotechnology, viral vectors, monoclonal antibodies, and stem cells. Machine learning and artificial intelligence are also being explored for their potential assistance in managing the disease.
What else can Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease)) be?
- Conditions similar to Lower Motor Neuron Disorders:
- Benign fasciculations (non-harmful muscle twitches)
- Inclusion body myopathy (a muscle disease)
- Multifocal motor neuropathy (nerve damage leading to muscle weakness)
- Monomelic amyotrophy (muscle weakness and wasting in a single limb)
- Neuralgic myopathy (muscle pain and weakness)
- Hirayama disease (disease involving muscle weakness and wasting)
- Spinobobulbar muscular atrophy (a genetic condition causing muscle wasting)
- Distal spinal atrophy syndrome (also known as Charcot-Marie-Tooth disease, a genetic disorder affecting the nerves)
- Conditions similar to Upper Motor Neuron Disorders:
- Hereditary spastic paraplegia (a group of inherited disorders that cause leg stiffness and weakness)
- Adrenomyeloneuropathy (a rare genetic condition that affects the nerves)
- Late-onset Tay-Sachs disease (a rare genetic disorder)
- Polyglucosan body disease (accumulation of abnormal substances in body organs)
- HIV myelopathy (spinal cord disease associated with HIV)
- Multiple sclerosis (immune system attacks the protective covering of nerves)
- Myasthenia gravis (long-term neuromuscular disease)
- Nutritional myeloneuropathies (nervous system disorders caused by nutritional deficiencies)
- Post-polio syndrome (a condition that affects polio survivors years after recovery from an initial acute attack)
- Conditions showing both Lower and Upper Motor Neuron signs:
- Cervical radiculomyelopathy (a condition involving nerve root compression in the neck)
- Hyperthyroidism (a condition where your thyroid gland produces too much of certain hormones)
- Respiratory decline requiring ventilatory support
- Difficulty swallowing (dysphagia)
- Difficulty speaking (dysarthria)
- Malnutrition
- Muscle spasms
- Stiffness (spasticity)
- Fatigue
- Functional decline due to muscle weakness
- Excessive saliva (sialorrhea)
- Thick mucus secretions
- Pseudobulbar affect (sudden, inappropriate emotional reactions)
- Aspiration pneumonia
- Respiratory insufficiency
- Gastrointestinal upset and arrhythmias from Mexiletine
- Liver inflammation and fatigue from Riluzole
- Gait disturbances and headaches from Edaravone
What to expect with Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
ALS, or Amyotrophic Lateral Sclerosis, currently has no cure. On average, those diagnosed with the disease typically live 3 to 5 years. Close to 30% of patients might live up to 5 years, and around 10% could reach ten years. Two drugs, Riluzole and Edaravone, have shown some benefit; Riluzole may extend life by 3 months on average, and Edaravone can potentially slow the disease’s progression by a third in 6 months.
Various factors may influence how long an ALS patient might live. These include carrying some extra weight at the time of diagnosis, being younger when the disease starts, having a higher functional rating (indicating a lower level of disability), better lung function (forced vital capacity), and limb symptoms rather than symptoms affecting speech or swallowing (bulbar symptoms). Some patients with a specific type of ALS called flail-arm syndrome usually live longer. Certain genetic variants like SOD1, TARDP, EPHA4, and FUS/TLS mutations can impact the disease progression and survival as well.
On the other hand, the disease may progress more aggressively in patients who were older at the start, had a quick transition from first symptoms to diagnosis, and needed non-invasive ventilation (a type of breathing support) early. Specific genetic mutations like A4V and P525L may also lead to accelerated progression of the disease and a shorter lifespan.
Possible Complications When Diagnosed with Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
Amyotrophic lateral sclerosis, or ALS, can lead to a variety of complications. These include declining lung function that may require breathing support, difficulty swallowing and speaking, malnutrition, muscle spasms, stiffness, fatigue, and declining ability to move due to muscle weakness. Other issues may include excessive saliva, thick mucus, and sudden, inappropriate emotional reactions, known as pseudobulbar affect. The most common causes of death in people with ALS are aspiration pneumonia and respiratory insufficiency. There can also be complications caused by medications used to manage the symptoms of the disease. For instance, Mexiletine can cause upset stomach and irregular heart rhythms. Riluzole can lead to liver inflammation and fatigue. Edaravone can cause difficulties with walking and headaches.
Problems associated with ALS:
Possible medication side effects:
Recovery from Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
Acting quickly is key to get the most benefit in terms of movement and lifespan. It’s really important to do a thorough first check of balance, walking, muscle strength and stiffness, ability to tolerate activity, and how well day-to-day tasks are handled. To fight weakness and tiredness, it’s necessary to prevent falls through things like aids and changes to the environment, as well as learning how to save energy. Braces and other helpful tools can also be used to allow more independence in daily tasks.
It’s crucial for healthcare professionals, therapists, and caregivers to work together for the best treatment of the disease. The focus should be on understanding the progress of the disease, while making the patient as comfortable as possible, and improving their daily life. It’s also really important to teach patients and caregivers about the disease and to make sure they have the right social support.
Preventing Amyotrophic Lateral Sclerosis (Amyotrophic Lateral Sclerosis (Lou Gherig Disease))
Amyotrophic Lateral Sclerosis (ALS) is a disease that gradually worsens over time, leading to muscle weakness. It affects most muscles in the body as it progresses. Some people might inherit this disease from their family, but most people get it for various other reasons. Symptoms often start mildly, affecting just one arm or leg, or causing challenges with speaking, swallowing or breathing. However, over time, all patients will experience weakening of muscles that assist with swallowing and breathing, and will need help with meals and breathing.
After being diagnosed with ALS, an individual typically lives for 3 to 5 years, although some surpass this average timing. Managing ALS involves a team of healthcare professionals including speech therapists, occupational therapists, physical therapists, neurologists, nurses, respiratory therapists, dieticians, palliative care providers, and social workers. It can be quite overwhelming to receive an ALS diagnosis, but patients who receive care from a multi-faceted team at an ALS clinic tend to live longer compared to those who are treated by a single healthcare provider.
Currently, there is no cure for ALS. However, several medications and management strategies are available to extend survival and relieve symptoms. These measures help in making the life of the patient more comfortable and manageable.
