Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Diagnosing ALS requires a combination of tests to rule out other possible conditions and confirm the presence of key signs of ALS.
Overview of ALS Diagnosis
There is no single test that can definitively diagnose ALS. Doctors arrive at an ALS diagnosis by combining the results of a thorough medical history, physical exam, series of tests, and careful exclusion of other diseases. The main steps are:
- Taking a complete medical history and performing a neurological exam
- Conducting tests to rule out other diseases
- Evaluating signs and symptoms to check for upper and lower motor neuron damage
- Tracking disease progression over time
Some key signs doctors look for are muscle weakness, wasting, cramping and twitching (fasciculations); difficulty speaking (dysarthria) or swallowing (dysphagia); and reduced reflexes. Doctors need to establish that motor neuron damage is occurring in multiple body regions to support an ALS diagnosis.
Medical History and Neurological Exam
The first step in checking for ALS is taking a complete medical history and performing a neurologic exam. The doctor asks about:
- Onset, progression, and pattern of symptoms
- Parts of the body affected
- Changes in speech, swallowing, balance, coordination
- Muscle weakness, twitching, cramping
- Changes in thinking or behavior
- Relevant family history
In the neurological exam, the doctor checks physical signs like:
- Muscle strength, mass, tone
- Reflexes
- Babinski reflex (stimulating the sole of the foot)
- Changes in speech and tongue movement
- Breathing tests
This information helps the doctor map out where nerve damage may be occurring and narrow down the possible diagnoses.
Ruling Out Other Diseases
Since there is no definitive ALS test, doctors must rule out a number of other conditions that can mimic ALS symptoms, including:
- Spinal muscular atrophy (SMA) – weakness and wasting of muscles due to loss of lower motor neurons
- Multiple sclerosis (MS) – damage to the protective nerve fibers that causes motor and sensory problems
- Multifocal motor neuropathy – progressive asymmetric weakness without sensory loss
- Polymyositis – muscle inflammation and progressive weakness
- Inclusion body myositis – inflammatory disorder affecting muscle
- Peripheral neuropathy – damage to peripheral nerves causes weakness and numbness
- Cervical spondylosis – degenerative disc disease in the neck compressing spinal cord
Doctors may conduct a variety of tests to help rule out other conditions, including:
- Blood tests: Check for signs of inflammation, antibodies, vitamin deficiencies, infections, thyroid problems, etc.
- Creatine kinase test: Measures level of muscle enzyme in blood, which can indicate muscle damage.
- MRI:Generates images of the brain and spinal cord to check for MS, tumors, injuries, or structural problems.
- Nerve conduction studies: Measure how quickly electrical signals move through a nerve. Can detect nerve damage consistent with neuropathies.
- EMG (electromyography): Records electrical activity of muscles at rest and during contraction. Assesses nerve-muscle connectivity.
- Lumbar puncture (spinal tap): Removes CSF fluid to check for infection, inflammation, blood, or cancer cells.
Checking for Evidence of Upper and Lower Motor Neuron Damage
The presence of both upper and lower motor neuron damage is a key diagnostic sign of ALS. Doctors assess this damage in a few ways:
Signs of Lower Motor Neuron Damage
- Weakness and wasting of muscles
- Twitching and cramping of muscles (fasciculations)
- Reduced muscle tone
- Decline in reflexes
Signs of Upper Motor Neuron Damage
- Stiffness and tightness of muscles (spasticity)
- Overactive reflexes
- Abnormal reflexes like the Babinski reflex
- Changes in speech and swallowing
ALS nearly always starts with lower motor neuron damage before upper motor neuron signs emerge. Doctors have to monitor patients over time to detect both types of involvement.
Tracking Progression Over Time
Since ALS symptoms generally worsen gradually after initial onset, doctors need to monitor progression over a period of months to confirm that muscle weakness and motor deficits are spreading to new parts of the body. This helps establish that the damage is ongoing rather than limited to one area or incident.
Some tools used to track changes over time include:
- Strength testing – repeated manual muscle testing
- ALSFRS-R scale – survey of daily functioning abilities
- Pulmonary function tests – check for respiratory muscle decline
- Swallowing studies – assess swallowing safety and effectiveness
Seeing new regions and motor neuron groups affected on follow-up assessments strengthens the case for an ALS diagnosis. Progression that fits with ALS includes:
- Muscle weakness spreading to new limb or site within 3-6 months
- Progression from asymmetric to bilateral involvement
- Emergence of both upper and lower motor neuron signs
- Worsening speech, swallowing, breathing difficulties
Supporting Tests
In addition to the main diagnostic steps, certain other tests can provide supporting evidence for ALS, even though they aren’t definitive on their own. These include:
Electromyography (EMG)
An EMG tests the electrical activity of muscles during rest, slight contraction, and forceful contraction. It can detect abnormal muscle electrical discharges (fibrillations) and fasciculations that signal nerve damage. However, EMG only detects ongoing denervation – it cannot confirm prior motor neuron loss in unaffected muscles.
Nerve Conduction Studies
Nerve conduction studies measure how fast electrical impulses travel along motor and sensory nerves. Slowed nerve signals can indicate nerve damage. But normal conduction velocity does not rule out motor neuron disease.
MRI of Brain and Spinal Cord
MRI scans create detailed images that can reveal structural problems or abnormalities like tumors, spinal cord compression, or vascular malformations. But MRI cannot visualize motor neurons themselves. About 90% of ALS patients have a normal MRI.
Muscle Biopsy
Removing a small sample of muscle tissue for microscopic analysis can confirm nerve fiber degeneration and muscle changes consistent with denervation. But it cannot prove motor neuron damage in the brain or spinal cord.
Genetic Testing
Testing for known ALS-linked genes like C9orf72, SOD1, TARDBP, and FUS identifies an ALS-causing mutation in 5-10% of cases. But most cases have no known genetic cause.
ALS Mimics
In some instances, the doctor will determine that a patient has a disease that mimics ALS. Motor neuron disorders that may be mistaken for ALS include:
Primary Lateral Sclerosis (PLS)
PLS mainly affects upper motor neurons. It progresses much slower than ALS and life expectancy is near-normal. There is no effective treatment but the course is less aggressive.
Progressive Muscular Atrophy (PMA)
PMA involves only lower motor neuron damage leading to muscle weakness. Progression is slower than ALS and does not spread to all limbs. Some patients live 10-20 years.
Monomelic Amyotrophy (MMA)
A benign motor neuron disease mostly affecting a single limb before age 50. It does not spread elsewhere and leaves life expectancy unaffected.
Conclusion
There is no single definitive test for ALS – an experienced neurologist makes the diagnosis by:
- Thoroughly assessing symptoms and their progression
- Excluding alternative diagnoses
- Confirming evidence of widespread motor neuron damage
- Tracking gradual worsening consistent with ALS
Proper diagnosis often takes 6-12 months. Tests like EMG, MRI, and genetic testing contribute supporting evidence. Regular follow up helps confirm that damage is spreading in a pattern consistent with ALS. While ALS has no cure, early diagnosis assists with lifestyle planning and starting maximal symptom management.