ALS diagnosis

Confirming a diagnosis of amyotrophic lateral sclerosis (ALS) is typically a complex process that involves testing for signs indicative of the progressive neurodegenerative disease and ruling out other potential disorders that could cause similar symptoms.

There is no definitive test for ALS, which usually begins in patients between the ages of 55 and 75. Instead, the ALS diagnosis process is based on a period of observation to track symptom progression, combined with a series of clinical tests to exclude other conditions. It generally takes about 10-16 months from the onset of symptoms before a diagnosis of ALS is confirmed.

Diagnostic criteria

Also known as Lou Gehrig’s disease, ALS is caused by the nerve cells that control movement (motor neurons) becoming progressively damaged and dying. Motor neurons in both the brain and spinal cord — upper and lower motor neurons — are affected.

Damage to upper motor neurons typically causes symptoms such as muscle stiffness and overactive reflexes, while the degeneration of lower motor neurons results in weakness, muscle atrophy (wasting), and muscle twitches.

Historically, the El Escorial criteria of the World Federation of Neurology served as the standard for ALS diagnosis. In recent years, however, clinicians have shifted toward a new set of recommendations called the Gold Coast criteria. In research and clinical settings, patients may still see both sets of ALS diagnostic criteria being used.

El Escorial criteria

The El Escorial criteria were initially published in 1994 and have since been updated multiple times. According to the last formal major update of the criteria in 2000, an ALS diagnosis requires:

• signs of progressive degeneration in both upper and lower motor neurons
• evidence of disease progression, meaning symptoms worsening over time and spreading to new areas
• exclusion of other conditions that might explain symptoms via imaging and lab tests

Based on the strength of the findings, a person is labeled as having definite, probable, or possible ALS or not having the disease.

While these criteria are good at preventing a mistaken ALS diagnosis in someone without the disease, they were criticized because their stringency could miss some ALS cases and exclude people from participation in clinical trials. In 2015, researchers proposed simplifications to facilitate diagnoses, which helped pave the way for the Gold Coast criteria.

Gold Coast criteria

The Gold Coast criteria, emerging in 2020, were designed to provide a simpler, more clinically practical diagnostic framework. Under this system, there is no “possible” or “probable” ALS — a person is deemed to either have or not have the disease.

As with the El Escorial criteria, disease progression (worsening motor symptoms) and exclusion of other conditions are still required. However, these criteria do not require signs of upper motor neuron dysfunction if there is evidence of lower motor neuron dysfunction in at least two body regions.

Experts believe that these updates are more sensitive to catching early signs of ALS and will help maximize patient eligibility for clinical trials.

What tests are used to diagnose ALS?

For a full ALS diagnosis, a doctor will thoroughly examine a person’s medical and family history and perform a complete neurological assessment. A number of clinical tests are then usually needed to identify characteristic signs of motor neuron degeneration and rule out other conditions that can cause similar symptoms.

Throughout the process, individuals will work closely with their ALS care team to prepare for ALS testing and understand their ALS test results.

Clinical tests

A neurologist’s ALS evaluation will likely involve several tests, including:

• electrodiagnostic tests: evaluate nerve and muscle function, including nerve conduction studies (NCS) and electromyography (EMG)
• imaging tests: visualize changes in the brain, spinal cord, or muscle tissue
• spinal tap: looks for abnormalities in the cerebrospinal fluid that circulates around the brain and spinal cord
• blood or urine tests: identify ALS-related genetic mutations and rule out other disorders
• muscle and nerve biopsies: identify cellular changes in muscles or nerves

NCS involves stimulating a nerve with a small electrical shock and recording the response of a muscle it controls, while EMG involves inserting a small needle electrode into a muscle to record its electrical activity. The observed pattern of changes in nerve and muscle signaling can help doctors identify signs of motor neuron dysfunction consistent with ALS and rule out other conditions.

Imaging tests, including MRI scans, are mainly used to rule out other neurological diagnoses. Brain and spinal cord MRI is largely normal in most ALS cases.

Spinal taps, and blood and urine tests can be used to identify other conditions that may be causing symptoms, as well as signs of muscle or nerve damage and inflammation. Biopsies, in which a sample of affected tissue is collected and examined under a microscope, are typically performed only in complex or atypical cases where other tests are inconclusive.

A blood sample can also be used for genetic testing to identify mutations linked to some cases of ALS. This is usually done in cases of familial ALS, where the disease runs in the family. However, genetic mutations are not found in everyone with the disease, so genetic testing for ALS alone cannot confirm or rule out a diagnosis.

Differential diagnosis

Through these tests, doctors should be able to rule out conditions that mimic ALS. Some of the conditions that might be considered in an ALS differential diagnosis are:

• autoimmune and inflammatory diseases like myasthenia gravis, multiple sclerosis, Guillain-Barré syndrome, and multifocal motor neuropathy
• genetic conditions, including forms of spinal muscular atrophy and muscular dystrophy
• infection-related problems such as HIV or post-polio syndrome
• nutritional problems like vitamin B12 or copper deficiency
• hormonal issues, including thyroid problems
• other neurological conditions like Parkinson’s disease, stroke, or spinal cord injury

These are just some of the diseases that can be mistaken for ALS, which is why the diagnosis can take so much time. Prompt referral to a neurologist specializing in ALS and related conditions can expedite diagnosis, avoid diagnostic delays, and prevent misdiagnosis.

Because the diagnosis can be so complex, the ALS Association also recommends getting a second opinion after an initial diagnosis.

Steps and support after receiving an ALS diagnosis

Patients should work closely with their care team to determine what happens after an ALS diagnosis. This will generally include discussions about treatment, including medications that may slow ALS progression, as well as interventions and lifestyle changes to ease symptoms and improve quality of life.

Living with ALS takes a heavy emotional toll on patients and their loved ones. Therapy or support groups, available in-person or online, can help individuals cope with the impact of ALS symptoms and diagnosis.

As ALS is a severe disease that usually causes substantial physical disability and death within a few years of symptom onset, the next steps after diagnosis will also usually include discussions about the patient’s desires regarding life support and end-of-life care. These conversations can be emotionally taxing, but they are critical to ensuring the patient’s wishes are carried out, even when communication becomes difficult or impossible.