The diagnosis rarely turns out to be incorrect for the vast majority of patients diagnosed with amyotrophic lateral sclerosis (ALS) by a neurologist with expertise in ALS. Nonetheless, the following list of conditions deserves consideration because rare patients with these diseases may be confused with ALS.

  • Cervical spine diseaseL: pinching of the nerves of the spinal cord
  • Spinal muscular atrophy, Kennedy’s disease: gene abnormalities causing cell degeneration
  • Radiation damage
  • Syringomyelia: fluid sac in the spinal cord
  • Hyperthyroidism and hyperparathyroidism: increased activity of the thyroid and parathyroid glands
  • Multifocal motor neuropathies or chronic inflammatory neuropathies: inflammation of the motor nerves
  • Lead or mercury intoxication
  • Lymphoma, Hodgkin’s disease: forms of cancer
  • Hexosaminidase deficiency: an enzyme important in nerve cell metabolism
  • Post-polio syndrome: weakening that can occur 25 to 40 years after the original polio attack
  • Lyme disease: caused by a bite from an infected tick
  • Syphilis

Other motor neuron diseases that may mimic ALS and may be inherited include spinal muscular atrophy as well as spinobulbar muscular atrophy (Kennedy’s syndrome). Both of these diseases are very slow and gradual in their development, and they tend to be quite symmetrical, without the striking difference from one side of the body to the other side that is often seen in ALS. Kennedy’s syndrome preferentially affects men and may affect the speech and swallowing muscles, as well as the limb muscles; there may be prominent twitching and thinning of the muscles, all similar to ALS. There are no upper motor neuron abnormalities in Kennedy’s syndrome; other abnormalities are present including excessive breast tissue, small testicles, and numb or tingling feet. Spinal muscular atrophy is a very gradually evolving weakness of the limbs that mainly involves the lower motor neurons. Weakness and thinning in a symmetrical pattern may start at any age in both men and women.

Perhaps the most common condition that can mimic ALS is arthritis in the spine, either within the neck (cervical region) or in the low back (lumbar region). Pinching of nerves or the spinal cord may produce signs and symptoms that can be confused with ALS. Patients with disease of the spine may have lower motor neuron abnormalities, which may or may not be painful, accompanied by disturbed sensory function. Disturbance of bladder and bowel control (uncommon in ALS) and upper motor neuron signs in the legs are common in people with compression of the spinal cord from cervical spine disease. Magnetic resonance imaging (MRI) of the spine is the easiest way to evaluate the possibility of cervical or lumbar spine disease. The spinal cord may also be abnormal when there is a collection of fluid called a syrinx compressing the nerves. This rare abnormality is easily visualized on MRI. Any history of radiation directed toward the nerves or spinal cord that can cause degeneration in the motor neurons and the spinal cord should be carefully considered in terms of a cause of the patient’s symptoms and signs.

Hormonal disorders, particularly those affecting the thyroid gland, may cause symptoms and signs that can be confused with ALS. When the thyroid gland is overactive, muscles may become thinned and weakened. All patients suspected with ALS should have thyroid function testing. Parathyroid abnormalities are rare, but they may also cause both lower motor neuron and upper motor neuron disturbances, although most patients have bone pain, numb feet, and trouble with thinking.

Patients with late onset multiple sclerosis that comes on very gradually and very slowly may also be confused with ALS. Imaging (MRI) and spinal fluid analysis and evoked response tests can usually clarify the situation.

Disorders of the immune system may cause abnormalities in the nerves that can mimic ALS. A very slowly progressive neuritis called multifocal motor neuropathy, caused by inflammation in the nerves, may occasionally be confused with ALS. This condition evolves extremely slowly in most patients over many years and it is rarely confused with ALS by experts. It is potentially treatable with intravenous immunoglobulin infusions. Occasionally, patients with another disorder caused by inflammation in the nerve cells called chronic inflammatory polyneuropathy may have so little in the way of sensory symptoms that they may be confused with ALS. This treatable condition is never associated with upper motor neuron signs, and electrodiagnostic studies document marked slowing of nerve impulses virtually never seen in ALS.

Occasionally, patients may have a toxic exposure that can mimic ALS, but this is indeed rare. Patients with lead intoxication who may develop weakness in the hands and feet are extremely rare, but this should be tested if there is a history of excessive lead exposure. The same is true of mercury intoxication, which is a very rare cause of confusion in patients suspected of ALS.

Some types of malignancy, such as leukemia, Hodgkin’s disease, and lymphoma, are occasionally seen in patients with true ALS. Most of these patients have both upper motor neuron and lower motor neuron abnormalities, and the tumors may either be identified before or after ALS symptoms develop. In a very small percentage of patients, therapies to treat the tumor may help the ALS. There is a need for much more research in this particular area.

Analysis of an enzyme called hexosaminidase A (important in nerve cell metabolism) should be considered in patients who develop an ALS-like syndrome below the age of 30, because a deficiency of this enzyme may cause a condition mimicking ALS.

Patients who have had polio may develop a syndrome of increasing weakness 20 to 40 years after the original disease. Occasionally these patients develop ALS, perhaps unrelated to their prior polio, but most only have a modest worsening of the prior symptoms of polio. There is no specific  treatment for this condition at this time.

Occasionally a muscle disease called inclusion body myositis may be mistaken for ALS. This is a common inflammatory muscle disease of older adults that causes weakness and muscle thinning. An electromyogram (EMG), which tests the electrical activity of muscles, may be sufficient to distinguish this muscle disease from the muscle abnormalities seen in ALS. A muscle biopsy is needed when there is a clinical suspicion of a muscle disease.

Infectious diseases rarely can mimic ALS. There has been substantial concern about Lyme disease, but thus far, few if any documented cases of Lyme disease have truly mimicked ALS.