Diagnosing ALS involves conducting tests to exclude other conditions with similar signs and symptoms. There are no widely accepted biomarkers, like blood tests, for ALS; instead, it is diagnosed after ruling out the presence of other diseases.
ALS is a progressive disease; tests are often repeated over time to monitor for signs of progression taking place.
Atrophy: the decrease in size or wasting of a body part.
Bulbar system: a group of structures in the brainstem that are involved in several essential functions, including motor control and autonomic regulation. The term "bulbar" refers to the medulla oblongata of the brain, which is shaped like a bulb.
Differential diagnosis: the process of identifying a condition by distinguishing it from other potential diagnoses that have similar symptoms.
Dysarthria: speech issues caused by weakness, paralysis, or lack of coordination of the muscles involved in speech production. It affects the physical production of speech.
Dysphagia: difficulty or discomfort in swallowing.
Dysphonia: a disorder of the voice, specifically relating to problems with voice production. It involves issues with the vocal folds (vocal cords) or the structures that control them.
Dyspnea: shortness of breath.
Fasciculations: involuntary movement of the muscles.
Hyperreflexia: an increased or overactive reflex response.
Motor neuron: a type of cell in the body that is responsible for transmitting signals from the brain to the muscles.
Orthopnea: difficulty breathing when lying down.
Spasticity: muscle rigidity or “stiffness”.
An individual experiencing fasciculations or muscle weakness and atrophy may ignore their symptoms for quite some time1. The individual eventually consults with a primary care physician when the symptoms become more serious. The primary care physician may first order certain diagnostic tests, such as urinalysis and blood tests. A referral to a specialist is made if the primary care physician is sufficiently concerned about the symptoms and there is no clear indication of the cause.
I ignored the fasciculations in my arms for months before finally telling my family doctor. She wasn't overly concerned, and neither was I. Another few months went by before it finally became disruptive to my sleep, and I started to think something might be wrong. I explained this to my doctor, and she referred me to a neurologist.
– Man diagnosed with ALS at age 38
A neurologist begins diagnostic work-up with a consultation about the symptoms. Questions about when the symptoms occur, their scale and significance, what parts of the body they occur in, and questions about family history are asked2.
At some point following an initial consultation, most neurologists perform a neurological exam, which is a large set of tests aimed at determining the health of the individual's nervous system. Vision, hearing, balance and coordination, responses to sensory input such as temperature and vibration, and mental state are among some of the aspects of the exam3. An individual with ALS may have abnormal reflexes and difficulties with certain movements; otherwise their neurological exam will likely be unremarkable4. Abnormalities in sensory responses weakly suggest that the symptoms are caused by something other than ALS5.
Part of the initial consultation for an individual with symptoms in their limbs will involve measuring strength of muscles known to be affected, along with a broad selection of other muscles. The results of these measurements indicate to the neurologist which nerves may be affected6. Symptoms which are only present in a single nerve would suggest peripheral neuropathy, though this would not be conclusive in the early stages of diagnosis7.
Electromyography (EMG) and nerve conduction study (NCS) are likely to be performed early on in the diagnostic process8. The EMG and NCS results may not be abnormal when first conducted; it may take several months or years for further indication of disease to become apparent.
The neurologist I was referred to did a needle EMG and nerve conduction study on my first visit, after a quick neurological exam. When I got the results back, it didn't look like anything serious was going on. I used computers a lot, and had some issues with my elbows, which showed up on the nerve conduction study, but it was not overly concerning.
It was not until another round of testing three months later that we started to see that there had been more progression. After another three months, we finally had established a clear trend that something serious was going on. In that time, my hands were getting weaker, and the fasciculations in my arms and a few other places were becoming more intense. But other than that, I still seemed healthy and I was carrying on with my life.
– Man diagnosed with ALS at age 38
X-ray or MRI imaging are used to determine if there are any obvious signs of nerve compression. Blood, urine, and tissue samples are taken if not taken previously. Blood tests are often expanded to include heavy metals or diseases such as Lyme disease.
Unremarkable imaging and laboratory testing supports an ALS diagnosis9.
Treatments for autoimmune disorders with ALS-like symptoms are administered on occasion in an attempt to at least partially rule out the presence of such a disease; failure to respond to such treatments supports an ALS diagnosis10.
After three rounds of needle EMG and nerve conduction studies, which showed progressively worsening results, combined with numerous other tests like bloodwork and MRI—all of which returned negative results—my neurologist began to seriously consider ALS as a likely diagnosis. Still, it took another few months before the ALS diagnosis was finally made.
– Man diagnosed with ALS at age 38
This section has not been completed.
This section has not been completed.
Imaging such as x-ray, magnetic resonance imaging (MRI) and ultrasound may be employed11.
Magnetic Resonance Imaging (MRI) is a diagnostic imaging technique that uses magnetic fields and radio waves to form images of the inside of the body. The patient is placed in a large machine called an MRI scanner for 5 to 30 minutes, depending upon the size of the area being scanned. Unlike x-ray, the patient is not exposed to significant levels of radiation.
MRI of the brain, brainstem and spine are used to determine the presence of the following:
MRI of the cervical spine may involve positioning of the head and neck so as to deliberately cause movement of the vertebrae in such a way that nerve compression may occur, as seen in Monomelic Amyotrophy (Hirayama Disease)12.
Images obtained from MRI may appear normal in the early stages of ALS; in the later stages, changes may become more noticeable13.
Ultrasound can be used to observe fasciculations in the muscles, and to observe function of the thoracic diaphragm muscle, used for breathing14.
X-ray may be used in the early stages of patient encounters with primary care physicians; however, a neurologist will typically use MRI and ultrasound for imaging needs15.
Electrodiagnostic testing refers to a group of diagnostic tests used to evaluate the function and health of muscles and nerves. These tests involve the use of electrical impulses to assess the electrical activity of nerves and muscles, helping clinicians diagnose and monitor various neurological and neuromuscular conditions.
Electrodiagnostic testing may be performed repeatedly if no affirmative diagnosis can be made. Subsequent testing which indicates a further loss of motor function is consistent with a diagnosis of ALS16.
Electromyography, or “Needle EMG” is a process whereby the electrical activity of muscles is monitored. The patient is asked to relax and contract individual muscles during the test. The physician observes the electrical signals on a screen which displays them in a wave form; audio feedback may also be present17.
An individual with ALS will likely have the following18:
Nerve conduction studies are used to determine the strength of the signals travelling across a distance along a nerve. Placement of the needle and electrode in various positions allow the physician to determine the specific site of an injury to the nerve, if one is present19.
Nerve conduction studies are performed in both the upper and lower limbs, so that comparisons can be made20. An individual with ALS may have an unremarkable nerve conduction study, though they may have slowing compound muscle action potential (CMAP)21.
Blood and urine studies are used to look for viral, fungal, or bacterial causes of symptoms.
High resolution serum protein electrophoresis, thyroid and parathyroid hormone levels and 24-hour urine collection for heavy metals are typically ordered22.
This section has not been completed.
This section has not been completed.
Main article: About ALS: Symptoms
Fasciculations, muscle weakness and atrophy, and spasticity are the primary symptoms targeted during a diagnostic work-up of ALS23. These symptoms may present in a variety of ways, such as limb weakness, or changes in speech.
Fasciculations are common and often have no known cause. Approximately 70% of people will experience fasciculations in their lifetime24. Benign Fasciculation Syndrome (BFS) is used to describe fasciculations of unknown cause; an individual with ALS may be diagnosed with BFS if fasciculations are the primary complaint, and muscle weakness and atrophy have not yet presented in significant magnitude.
Fasciculations may be visible to the naked eye by looking at the skin. They can also be observed using ultrasound and electromyography25.
This section has not been completed.
Muscles require innervation and motor signals from the brain to function and survive26. Muscle weakness and atrophy have the following fundamental causes27:
Causes of myopathy are divided into two distinct categories: inherited and acquired28. Inherited myopathy is present since birth, whereas acquired myopathy may appear at any time. Given the sudden appearance of ALS symptoms in adulthood, inherited myopathies are generally not considered during a diagnostic work-up of ALS29.
Myopathy diagnosis involves the use of blood tests, urine tests, and biopsies (tissue samples). Such tests would be unremarkable for an individual with ALS, unless they have comorbidities30.
Peripheral neuropathy refers to issues along the nerves themselves31. Nerve compression can slow or block nerve signals between the brain and muscles. Autoimmune disorders may attack the nerves. Lastly, diseases such as diabetes can cause nerve damage.
Peripheral neuropathy that only affects one nerve is called mononeuropathy; peripheral neuropathy that affect multiple nerves is called polyneuropathy.
Nerve compression will often cause sensory symptoms such as tingling along with myopathy since most nerves carry sensory and motor nerve signals. Diagnostic imaging such as x-ray and MRI are used to visibly locate the site of compression; electromyography (EMG) and nerve conduction study (NCS) are used to locate the site of compression based on the behavior of the signals along the affected nerve32. Muscles which are innervated upstream of the nerve compression site should be unaffected33.
Autoimmune disorders can harm nerves in the following ways34:
Autoimmune disorders are diagnosed using blood tests, urine tests, and biopsies. Unremarkable test results do not definitively prove the absence of autoimmune disorders35.
Some autoimmune disorders, such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Guillain-Barré syndrome, are treatable using Intravenous Immunoglobulin (IVIG). IVIG is an intravenous treatment containing antibodies from thousands of healthy blood donors. IVIG treatment is not always successful; a failed treatment course does not definitively disprove the presence of an autoimmune disorder nor prove ALS36.
Muscle weakness and atrophy that is not a consequence of myopathy or peripheral neuropathy may be caused by a disease of the motor neurons themselves37. ALS is such a disease.
Degeneration of motor neurons inhibits the transportation of motor signals from the brain to the muscles. The absence of such motor signals causes muscle atrophy38. Muscle tissue will become scar tissue as the disease progresses39.
There are multiple diagnostic criteria defined for ALS. Different physicians may use one over another, depending on a variety of factors such as when they were educated, their confidence in the defined criteria, and the policies of the institution that they work in.
The El Escorial diagnostic criteria was revised in 1998.
| Diagnostic category | Inclusion criteria41 |
|---|---|
| Definite ALS | Presence of upper motor neuron and lower motor neuron signs in three anatomical regions |
| Probable ALS | Presence of upper motor neuron and lower motor neuron signs in at least two regions with upper motor neuron sign rostral to lower motor neuron signs |
| Probable ALS, laboratory results supported | Presence of upper motor neuron and lower motor neuron signs in one region with evidence by EMG of lower motor neuron involvement in another region |
| Possible ALS | Presence of upper motor neuron and lower motor neuron signs in one region or upper motor neuron signs in two or three regions, such as monomelic ALS, progressive bulbar palsy, and primary lateral sclerosis |
The Gold Coast criteria was created at a 2019 conference in Gold Coast, Australia. A group of neurologists sought to improve upon existing diagnostic criteria, such as the El Escorial criteria.
Read about the Gold Coast criteria on PubMed:
| Table: diagnostic outcomes supporting an ALS diagnosis | ||
|---|---|---|
| Test or Procedure | Result supporting ALS | Result contradicting ALS |
| Blood testing | Unremarkable | Remarkable: infection or disease |
| Urine testing | Unremarkable | Remarkable: infection or disease |
| Neurological exam | Increased reflexes | Sensory symptoms, or symptoms indicating cognitive decline |
| Electromyography |
|
Unremarkable |
| Nerve conduction studies |
|
Abnormal findings for sensory nerves and/or motor nerves |
| MRI of brain, brainstem, and spinal cord |
Early stages: unremarkable Later stages: increased T2 signal as a white region in the posterior part of the internal capsule of the brain |
Visible brain damage, spinal cord injury, lesions |
| X-ray | Unremarkable | Visible nerve damage |
| Ultrasound | Visible fasciculations in multiple muscles innervated by distinct nerves | Unremarkable |
| IVIG treatment | No changes in symptoms | Recovery |