There is no single test that confirms Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS). Diagnosis relies on a combination of neurological exams, electrical nerve testing, lab work, and imaging, all working together to identify a pattern of nerve damage while ruling out other conditions that can look similar. The process typically takes about 11.5 months from the first symptom to a confirmed diagnosis, with many people seeing multiple doctors along the way.
Why Diagnosis Takes So Long
ALS begins subtly. Early symptoms like a weak grip, tripping while walking, or slurred speech overlap with dozens of other conditions. Many people initially receive a different diagnosis before being referred to a neurologist who specializes in motor neuron diseases. Misdiagnosis is relatively common in the early stages, and some people go through multiple rounds of testing and second opinions before getting a definitive answer.
The median time from first symptom to confirmed diagnosis is 11.5 months, though the range is wide. Some people get answers in seven months, while others wait 20 months or longer. Part of this delay is built into the diagnostic criteria themselves: doctors need to document that symptoms are progressing over time, which requires repeat visits. The other part comes from the extensive testing needed to exclude other causes.
The Neurological Exam
ALS damages two types of nerve cells at the same time: upper motor neurons (which run from the brain down the spinal cord) and lower motor neurons (which run from the spinal cord out to the muscles). The physical exam looks for signs of damage in both systems, because this combination is what sets ALS apart from most other conditions.
Upper motor neuron damage produces stiff, tight muscles, exaggerated reflexes, and slow or poorly coordinated movements. Your doctor may check for the Babinski sign (where the big toe fans upward when the sole of the foot is stroked) or the Hoffman sign (an involuntary finger flick triggered by snapping the tip of the middle finger). Lower motor neuron damage looks different: muscles become weak and visibly shrunken, reflexes may be absent, and you may notice fasciculations, the small involuntary twitches that ripple under the skin.
Under the current Gold Coast diagnostic criteria, a doctor needs to find upper and lower motor neuron dysfunction in at least one body region. The body is divided into four regions for this purpose: bulbar (face, tongue, and throat), cervical (arms and hands), thoracic (trunk muscles), and lumbosacral (legs and feet). If only one region shows problems, both upper and lower motor neuron signs must appear in that same region. If upper motor neuron signs are absent, lower motor neuron dysfunction must appear in at least two regions.
Electromyography (EMG)
EMG is one of the most important diagnostic tools for ALS. It uses thin needle electrodes inserted into muscles to record their electrical activity, revealing nerve damage that may not yet be visible on a physical exam. The test can detect problems in muscles that still feel normal to you, which helps doctors map how widespread the disease process is.
In ALS, EMG shows two things happening simultaneously. First, there are signs of active, ongoing nerve damage: fibrillation potentials and positive sharp waves, which are tiny spontaneous electrical discharges from muscle fibers that have lost their nerve supply. Fasciculation potentials, the electrical signature of those visible muscle twitches, also count as evidence of active nerve loss. Second, there are signs the body is trying to compensate. When some motor neurons die, neighboring healthy neurons sprout new branches to take over the orphaned muscle fibers. This remodeling creates abnormally large, long electrical signals called motor unit potentials. These oversized, often jagged signals are a hallmark of chronic nerve damage with attempted repair.
Your doctor will typically test muscles in several body regions during the same session to see how many areas are affected. The test takes 30 to 60 minutes and can be uncomfortable, though it’s not typically described as severely painful.
Blood Work and Spinal Fluid
Blood tests in an ALS workup aren’t looking for ALS itself. They’re designed to catch treatable conditions that can mimic it. Your doctor will likely check thyroid function, vitamin levels, markers of inflammation, and sometimes antibodies linked to autoimmune nerve diseases.
A lumbar puncture (spinal tap) serves a similar purpose. By analyzing the cerebrospinal fluid that surrounds your brain and spinal cord, doctors can check protein levels, antibody concentrations, and markers of inflammation. Elevated protein, abnormal antibody ratios, or signs of immune system activity in the spinal fluid would point toward inflammatory or autoimmune diseases rather than ALS.
One emerging blood marker is neurofilament light chain (NfL), a protein released when nerve cells are damaged. It’s elevated in most people with ALS, with reported sensitivity between 76% and 100%. However, NfL rises in many neurological conditions, not just ALS, so its specificity is limited. In specialized clinics, it tends to confirm what doctors already suspect rather than provide a breakthrough answer. Its main clinical value right now is helping gauge how active the disease is and tracking response in clinical trials.
MRI and Imaging
MRI of the brain and spinal cord plays a primarily exclusionary role. It can rule out structural problems like a herniated disc compressing the spinal cord, tumors, or multiple sclerosis lesions that could explain the symptoms. Cervical spondylotic myelopathy, where arthritis in the neck squeezes the spinal cord, is one of the conditions that can closely mimic ALS, and MRI is the best way to spot it.
In some ALS cases, MRI does show positive findings. The “motor band sign,” a dark line along the motor cortex of the brain on certain MRI sequences, reflects degeneration of upper motor neurons. A “bright tongue sign” can appear when tongue muscles are replaced by fat due to lower motor neuron loss. These findings can support a diagnosis, but their absence doesn’t rule ALS out.
Conditions That Mimic ALS
A critical part of the diagnostic process is making sure the symptoms aren’t caused by something else, particularly something treatable. In one population-based study, the most common ALS mimic was multifocal motor neuropathy, an autoimmune condition that causes progressive weakness without sensory loss and responds to treatment. It accounted for about 22% of cases initially misdiagnosed as ALS. Kennedy disease, a genetic condition that slowly weakens muscles and causes tremors, was the second most common mimic at 13%.
Other conditions that can look like ALS include myasthenia gravis, spinal muscular atrophy, certain thyroid disorders, and chronic inflammatory neuropathies. Nerve conduction studies, which are often done alongside EMG, help separate these conditions. In multifocal motor neuropathy, for example, nerve conduction tests reveal a specific pattern of blocked signals that doesn’t occur in ALS.
Genetic Testing
Current evidence-based guidelines recommend that all people diagnosed with ALS be offered genetic testing, regardless of whether they have a family history of the disease. This is a relatively recent shift. About 10% of ALS cases are considered familial, meaning there’s a known family history, but the same gene mutations can also appear in people with no affected relatives.
The recommended gene panel includes four genes in particular. The C9orf72 repeat expansion is the most common genetic cause of ALS in people of European ancestry, found in roughly 1 in 10 cases whether or not there’s a family history. SOD1 mutations are the second major target, and they carry special significance because a targeted therapy (an antisense oligonucleotide called tofersen) has received FDA approval specifically for SOD1-linked ALS. The panel also includes FUS and TARDBP, both of which have been identified in ALS populations worldwide and may qualify a person for clinical trials.
Genetic results don’t change the initial diagnosis, but they can open doors to specific treatments and help family members understand their own risk.
Getting a Second Opinion
Because ALS has no single confirmatory test and shares features with treatable conditions, seeking a second opinion from a neurologist who specializes in motor neuron diseases is a reasonable step. Final ALS diagnoses are typically made by specialized neurologists, often at academic medical centers or dedicated ALS clinics where doctors see the condition frequently. Some people initially diagnosed with ALS are later found to have a different motor neuron disease, such as primary lateral sclerosis, which progresses more slowly and affects only upper motor neurons. Others have their diagnosis confirmed but gain access to multidisciplinary care teams that can improve quality of life from the start.