Receiving an ALS diagnosis can be a long and difficult process. There is no one test that can determine if someone has the disease. To accurately diagnose ALS, doctors must identify the presence of ALS signs and symptoms while simultaneously ruling out diseases that mimic ALS.  

Some common diseases that must be ruled out when diagnosing ALS include other neurodegenerative diseases, viral or bacterial infections, cancers, and even spinal cord injuries.

Other Neurodegenerative Diseases

When diagnosing ALS, neurologists will look for evidence of the degeneration of both upper and lower motor neurons, as well as the clear progression of symptoms to other areas of the body. There are many other neurodegenerative diseases with similar symptoms to ALS, including:

  • Multiple Sclerosis (MS) – Multiple sclerosis is an autoimmune disorder in which the immune system attacks parts of the central nervous system, disrupting the brain’s ability to communicate with other parts of the body. This can lead to pain and weakness in the limbs, chronic fatigue, slurred speech, and paralysis.
  • Parkinson’s Disease – Parkinson’s disease, like ALS, causes the death of neurons. However, unlike ALS, this occurs almost exclusively in the brain. It often begins with a slight tremor in the hands, which gradually worsens. In later stages, it can cause slowed movement, muscle stiffness, trouble speaking and, eventually, trouble performing unconscious movements like blinking.
  • Huntington’s Disease – Huntington’s disease is a genetic condition that causes the progressive breakdown of most neuronal types in the brain. While this condition causes similar physical symptoms to ALS, it also comes with cognitive symptoms like confusion, loss of attention span, depression, anxiety, and increased irritability.  
  • Spinal Muscular Atrophy (SMA) – SMA is an inherited genetic condition that causes the progressive death of motor neurons in the brain stem and spinal cord, leading to difficulties with movement and muscle atrophy. The disease can be very serious in children and infants, while in adults it usually causes mild to moderate muscle weakness.
  • Multifocal Motor Neuropathy (MMN) – A disease in which, like MS, the immune system attacks some motor neurons, causing progressive weakness, as well as fasciculations (twitching) and muscle atrophy.  Unlike ALS, many cases of MMN can be effectively treated with IVIg. AN EMG test is important for distinguishing between MMN and potential ALS early in the diagnosis process.
  • Primary Lateral Sclerosis (PLS) – PLS is a very similar condition to ALS – in ALS, both the upper and lower motor neurons are affected, while PLS only involves exclusively upper motor neurons. Because of this, PLS leads to a similar loss of ability to control voluntary movements. It does not, however, affect involuntary movements such as breathing, and so is not always fatal. In many cases, people who have been diagnosed with PLS may later develop lower motor neuron symptoms, leading to a final diagnosis of ALS.
  • Hereditary Spastic Paraplegia (HSP) – HSP is a genetic condition which, like PLS, involves the upper motor neurons. Unlike PLS, it primarily affects the legs – causing spasticity (stiffness) and weakness. These symptoms will begin with mild trouble walking and advance until a walker or wheelchair is needed.

Early in the ALS diagnosis process, a neurologist will assess their patient’s symptoms to determine whether they are likely caused by another neurological condition. Electromyography (EMG) and Magnetic Resonance Imaging (MRI) tests can also be useful in ruling out these conditions.

Cancer

There are several cancers whose symptoms can mimic ALS. These include cancers of the brain and spine, which can cause difficulties with movement much like ALS. Other cancers like lymphoma, leukemia, lung cancer, and breast cancer can mimic ALS symptoms such as unsteadiness while walking, muscle stiffness, and weight loss.

MRIs, X-rays, and blood tests are important for ruling out these cancers while diagnosing ALS.

Viral and Bacterial Infections

Some diseases caused by viruses and bacteria can also cause similar symptoms to ALS, including:

  • Polio – Polio, a viral infection, is no longer a common disease thanks to vaccines. However, post-polio syndrome can develop years or decades after an infection. Like ALS, it can cause muscle and joint weakness, atrophy, and difficulty breathing or swallowing.
  • Lyme Disease – Lyme disease is a bacterial infection, usually passed through tick bites. If left untreated, Lyme disease can lead to neurological symptoms such as weakness, fasciculations, and facial paralysis.
  • HIV – HIV (human immunodeficiency virus) is the virus that causes AIDS (autoimmune deficiency syndrome). HIV attacks the immune system, weakening the body’s ability to protect against other infections. Additionally, HIV can enter the central nervous system by infecting immune cells that cross the blood brain barrier, which may trigger an inflammatory response that can damage the nervous system. This can lead to neurological complications affecting movement coordination and ability.

Blood tests may rule out infections as a potential cause of ALS-like symptoms during the diagnostic process. Doctors may also ask questions about a patient’s medical history to determine if they have been exposed to one of these diseases.

Other Conditions

  • Injuries – Many injuries to the brain, neck, and spinal cord, such as a herniated disc, can lead to ALS-like neurological and movement symptoms. An MRI test can rule these out during and ALS diagnosis.
  • Hyperthyroidism – Diseases causing an overactive thyroid gland can cause muscle weakness and tremors.  A blood test can rule out these conditions.
  • Heavy metal poisoning – Exposure to some heavy metals, such as lead, mercury, or arsenic can lead to pain and movement issues, as well as cognitive impairment. Chelation therapy, which uses drugs that bind to these metals to help remove them from the blood stream, can lead to the reversal of these symptoms in some cases.

How are researchers working to improve the ALS diagnostic process?

In addition to the tests available today, researchers are working hard to develop new, more accurate, and faster tests to diagnose ALS. At the ALS Therapy Development Institute (ALS TDI), a major goal of our ALS Research Collaborative (ARC) is to identify new ways to more quickly and accurately diagnose ALS.

Through our in-home blood collection program, we are searching for biological indicators (biomarkers) that can be detected through a simple blood test. Finding more reliable biomarkers of ALS progression or risk could potentially give clinicians new tools to diagnose the disease or even identify people who are at high risk of developing ALS before they show symptoms.

For more information about an ALS diagnosis, you can read more about the tests involved in the process here.

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