If you, or a family member or loved one, are experiencing muscle weakness, stiffness or cramps, you may be concerned about amyotrophic lateral sclerosis (ASL). This progressive disease affects nerve cells in the brain and spinal cord, causing a loss of muscle control.
Our guide will take you through the symptoms of ASl, what factors can contribute to developing the disease, and how MRI can help you get a diagnosis, so you can be sure of the next steps to take.
What is Amyotrophic Lateral Sclerosis (ALS)?
Amyotrophic lateral sclerosis (ALS), once known as Lou Gehrig’s disease, is a challenging and complex neurological condition that gradually affects how our muscles work. With ALS, the motor neurons (nerve cells in the brain and spinal cord) that allow us to move, speak, chew and breathe slowly deteriorate.
The degeneration of these neurons, particularly those in the lateral and anterior corticospinal tracts, means they lose the ability to communicate with the muscles, leading to muscle weakness, twitching (what experts call fasciculations) and eventually muscle shrinkage (atrophy).
Over time, the disease progression of ALS can affect white matter in the brain and spinal cord, making everyday actions and movements increasingly difficult as the brain loses control over voluntary movements.
ALS is relatively rare worldwide. On average, between 4 and 5 people in every 100,000 have ALS, but it can depend on where you live, your sex and how old you are. It’s the third most common neurological condition after Alzheimer's and Parkinson’s in Western countries. Men are slightly more likely to develop the condition than women, and although the disease can develop at any time, it’s more common in older people.
What Are the Symptoms of ALS?
The initial symptoms of ALS can be subtle and can vary from person to person. Since ALS is a progressive disease, symptoms tend to get worse over time.
The upper motor neurons (UMNs) and lower motor neurons (LMNs) are progressively damaged in ALS. UMNs originate in the brain and control voluntary movements by sending signals along the spinal cord to LMNs. LMNs in the spinal cord and brainstem then stimulate muscles to move.
When UMNs are damaged in ALS, muscles become stiff, and movements may feel clumsy or slow. Reflexes can become exaggerated, making muscles feel tight and hard to control. When ALS damages LMNs, muscles lose strength, start to twitch, and eventually shrink. This leads to weakness and difficulty with basic movements. The breakdown of UMNs and LMNs causes a unique mix of stiffness and weakness with ALS.
People with ALS may experience early symptoms of:
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Twitching in the arms, legs, shoulders or even the tongue (fasciculations)
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Muscle stiffness and painful cramps
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Muscle weakness in the arms, legs or neck
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Slurred speech (dysarthria)
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Difficulty chewing or swallowing food (dysphagia)
As the disease progresses, symptoms will become more pronounced, and may include:
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Difficulty with fine motor tasks such as buttoning shirts or picking up small items
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Excessive saliva production, causing drooling (sialorrhea)
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Sudden episodes of uncontrolled crying or laughing (pseudobulbar affect)
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Problems with the bladder or bowels
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Weakness in the legs or feet (foot drop) that causes stumbling or tripping
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Problems with balance and coordination
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Shortness of breath and difficulty breathing, eventually leading to respiratory failure
Will ALS Show on an MRI Scan?
While experts can’t use magnetic resonance imaging (MRI) to diagnose the disease directly, it is a crucial tool for excluding other conditions that have similar symptoms, like motor neurone diseases or Alzheimer’s disease. MRI helps to rule out diseases that mimic symptoms of ALS, such as multiple sclerosis or spinal cord tumours.
MRI can also show specific changes caused by ALS, particularly in the advanced stages of the disease. It can show shrinkage (atrophy) in areas of the brain and spinal cord that are affected by the degeneration of the motor neurons, atrophy in the motor cortex (the part of the brain that causes movement) and the spinal cord.
MRI is also used to help clinicians assess how severely the muscles are affected by MRI. Functional MRI (fMRI), a type of scan that measures and monitors brain activity by detecting blood flow) is also helpful in checking motor function as the disease progresses.
In summary, while MRI cannot diagnose ALS, it’s an important part of ALS diagnosis in that it helps your doctor rule out other conditions that could be causing your symptoms.
What Does ALS Look Like on MRI?
MRI that uses T2-weighted imaging can reveal areas of hyperintensity in the corticospinal tracts, which run from the motor cortex to the spinal cord. These will show up as brighter areas on MRI images. The internal capsule (an area of the brain where fibres of the corticospinal tracts are concentrated) is often the first area to show these areas of brightness. Over time, hyperintensity will spread down the corticospinal tracts.
MRI can also show iron buildup in the prescentral gyrus (an area within the motor cortex that controls voluntary muscle movement), a key sign of neurodegeneration. Depending on the type of MRI imaging used, this area may appear brighter or darker than surrounding brain tissue.
MRI using T1-weighted imaging may show hyperintensity and areas of brightness in the tongue area. This is most commonly seen in people who have difficulty talking and swallowing.
MR Spectroscopy is another MRI technique that looks at the chemicals in the brain and can help show how the brain changes as ALS progresses. It doesn’t create traditional pictures like regular MRI scans; instead, it provides a graph or spectrum that shows the levels of different chemicals in the brain. It’s a valuable tool for tracking disease progression.
Diagnosing Amyotrophic Lateral Sclerosis
Your clinician will take several steps to ensure that ALS is diagnosed and that other conditions or illnesses are ruled out. Here’s how they’ll do it:
Clinical Evaluation
The first step in diagnosing ALS is a thorough clinical evaluation. Your doctor will ask about your medical history and symptoms, including when they started, how they've changed, and whether there is a family history of ALS. They’ll also check if you have any other illnesses or health issues, which can help them determine which tests to recommend.
Neurological Examination
Your doctor will then carry out a neurological examination that checks how well your muscles are working, how your reflexes respond to stimulation and whether you feel things in the same way other people do. Your doctor will look for ALS symptoms, such as muscle weakness, stiffness, and overactive reflexes, which can be signs of the disease.
Electromyography (EMG)
Electromyography (EMG) is a test that helps diagnose ALS by checking the electrical activity in the muscles to see if the motor neurons are damaging them.
Nerve Conduction Studies (NCS)
Nerve conduction studies (NCS) happen alongside EMG to measure how well your nerves are working. They check how fast and strong the electrical signals move along the nerves. If you have ALS, your results are more likely to be normal because the disease primarily affects the motor neuron, not the nerves.
MRI of the Brain and Spinal Cord
MRI, as we’ve described, can help to rule out other conditions that mimic the symptoms of ALS, and it can show shrinkage in parts of the brain and spinal cord affected by ALS, especially in the later stages of the disease. Newer MRI techniques can also detect changes in the spinal cord, which can help with an ALS diagnosis.
Blood Tests
Your doctor will carry out a series of blood tests to help rule out other conditions that can cause muscle weakness, such as inflammation, thyroid problems or vitamin deficiencies.
Genetic Testing
If you have a family history of ALS, or you’re a younger person with signs of the disease, your doctor may recommend genetic testing so that they can confirm the diagnosis and give you information about how the disease may progress.
Cerebrospinal Fluid (CSF) Analysis
Sometimes, a doctor may wish to test the cerebrospinal fluid (CSF) with a lumbar puncture, to help rule out other neurological conditions and confirm ALS (if higher levels of certain proteins are in the CSF).
Muscle Biopsy (in rare cases)
Although this is rare, your doctor may recommend a muscle biopsy to rule out other muscle diseases. A biopsy will take a sample of muscle tissue and check it for changes that are specific to ALS.
What Are the Causes of Amyotrophic Lateral Sclerosis?
The causes of ALS can be complex and often involve a combination of genetic and environmental factors. However, here are some of the primary causes of ALS that experts have identified:
Genetic factors
Around 5-10% of ALS cases are inherited from family members (inherited or genetic ALS). Specific gene mutations are linked to ALS, including C9ORF72, SOD1, and TARDBP. These mutations lead to problems with how proteins in the body function, causing damage to motor neurons. In the last few years (2021), researchers have also found a unique form of genetic ALS that can affect children as young as 4, linked to the gene SPTLC1.
Environmental factors
In most cases of ALS (sporadic ALS), there are no single causes or risk factors, but environmental factors may play a role. Exposure to lead and pesticides may increase the risk of ALS, while head trauma has also been associated with ALS. Some studies have also suggested that how your generic makeup interacts with environmental exposure can impact the likelihood of developing ALS (2017). However, we need more research to be sure of all these factors.
What is the Treatment and Outlook for ALS?
Unfortunately, there is no cure for ALS or treatment to reverse the damage to motor neurons. Living with ALS can be challenging, but there are treatment options available to help slow the progression of the disease and improve quality of life.
The goal of treatment is to support you through each stage of this progressive condition, helping you to maintain independence and comfort for as long as possible.
Managing symptoms
ALS causes a wide variety of symptoms, such as muscle pain, cramps and stiffness. Medications such as baclofen and tizanidine can help to relax stiff muscles, while anticonvulsant drugs can relieve muscle cramps. You should also receive medication for pain relief.
Nutritional support
Because ALS can cause problems with chewing and swallowing, some people may have to have a feeding tube inserted, which delivers nutrition directly to the stomach. This will prevent malnutrition or dehydration.
Medicines to slow the progression of ALS
Riluzole can help slow the progression of ALS by controlling symptoms and extending survival in some people. The NHS is currently trailing edaravone, a medication that can help to slow the decline in physical abilities, but it is not available yet.
Respiratory support
As ALS progresses, it can weaken the muscles used for breathing, making breathing harder. Yur doctor may recommend non-invasive ventilation, which involves a machine that helps you breathe more easily. As the disease advances, invasive ventilation may be needed.
In terms of outlook, the course of ALS can vary from person to person. On average, people live 2 to 5 years after their diagnosis, but some can live longer with the right treatment and early intervention. Research continues to find better ways of predicting how the disease will progress, which can help doctors personalise treatments and find the best options for people living with ALS.
Differential Diagnosis to ALS
The following conditions have symptoms similar to ALS, and we’ve included how clinicians can help to differentiate these conditions from ALS.
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Multiple sclerosis (MS): MS is a condition where the immune system damages the protective covering of nerves, causing muscle weakness and spasticity, similar to ALS. However, MRI can reveal specific lesions in the brain and spinal cord, which are not seen in people with ALS.
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Chiari malformation: This condition occurs when part of the brain pushes down into the spinal canal, causing weakness, difficulty swallowing and other symptoms similar to ALS. An MRI can help to identify this, helping doctors tell it apart from ALS.
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Spinal muscular atrophy (SMA): A genetic disorder that causes weakness and muscle loss, usually starting in childhood or early adulthood. Unlike ALS, it has specific genetic causes, and doctors will diagnose it with electromyography tests that show a different pattern of nerve damage to ALS.
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Myasthenia gravis (MG): MG is an autoimmune disease where the body attacks the nerves that control muscles, causing fluctuating weakness and tiredness. MG can be diagnosed with blood tests, unlike ALS.
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Frontotemporal dementia (FTD): FTD can occur alongside ALS, especially when there are noticeable changes in memory, behaviour or personality. Brain scans (neuroimaging) may show shrinking in the front and temporal areas of the brain, which is different to what clinicians see in ALS-only cases.
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Other motor neurone diseases: Conditions such as progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS) also involve motor neurons but affect them differently. They cause symptoms similar to ALS but have different patterns of progression, which help to set them apart.
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Peripheral neuropathies: Conditions such as diabetic neuropathy or other nerve disorders can also cause muscle weakness and muscle loss. Tests such as nerve conduction studies can help show how the body’s nerves work, helping to rule out ALS.
Find an MRI Scan for Amyotrophic Lateral Sclerosis
If you’re worried that you or a loved one have symptoms of ALS, you can book a private MRI scan today, including a head and brain MRI. If you’re unsure whether an MRI is suitable for you, one of our expert clinicians is available for a personalised consultation. They can discuss your symptoms and concerns and help you decide what to do next.
Sources
ADORE (ALS Deceleration with ORal Edaravone) study. (2021). https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/adore-als-deceleration-with-oral-edaravone-study/
Amyotrophic Lateral Sclerosis (ALS). (2024). https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als
Amyotrophic lateral sclerosis. (2022). https://radiopaedia.org/articles/amyotrophic-lateral-sclerosis-3?lang=gb
Bonafede, R. and Mariotti, R. (2017). ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles. https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2017.00080/full
Brotman R.G., et al. (2024). Amyotrophic Lateral Sclerosis. https://www.ncbi.nlm.nih.gov/books/NBK556151/
Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing. (N.D.) https://www.als.org/navigating-als/resources/familial-amyotrophic-lateral-sclerosis-fals-and-genetic
Mohassel, P., et al. (2021). Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis.https://www.nature.com/articles/s41591-021-01346-1
Saccon, R.A., et al. (2013). Is SOD1 loss of function involved in amyotrophic lateral sclerosis?https://academic.oup.com/brain/article/136/8/2342/424144
