Amyotrophic lateral sclerosis

Diagnostic workup
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By Jinsy A Andrews MD and Hiroshi Mitsumoto MD

When encountering a patient with the clinical symptoms seemingly indicative of amyotrophic lateral sclerosis, the clinician needs to perform a diagnostic workup to exclude all other possibilities that may cause these clinical symptoms, thus, confirming the diagnosis. Electrodiagnostic tests, neuroimaging of the brain and spinal cord, laboratory studies, and muscle biopsies are useful tools to help the clinician diagnose accurately.

Electrodiagnostic tests. Electrodiagnostic studies are essential for the diagnostic workup in a patient with possible amyotrophic lateral sclerosis. They play important roles in identifying disorders that may resemble amyotrophic lateral sclerosis such as myopathy, neuromuscular transmission disorders, demyelinating polyneuropathy, plexopathy, or radiculopathy. Each of these disorders has typical findings in electrodiagnostic studies (Kimura 2001).

In 1969, Lambert proposed the electrodiagnostic test criteria, which included the following:

  1. Normal sensory nerve conduction studies
  2. Motor nerve conduction velocities, which are normal when recorded from relatively unaffected muscles and not less than 70% of the average normal value when recorded from severely affected muscles
  3. Fibrillation and fasciculation potentials in muscles of the upper and lower extremities or in the muscles of the extremities and the head
  4. Motor unit potentials reduced in number and increased in duration and amplitude (Lambert 1969).

The revised El Escorial criteria for amyotrophic lateral sclerosis require that the needle EMG examination show evidence of active and chronic denervation in at least 2 of 4 regions: (1) brainstem, (2) cervical, (3) thoracic, or (4) lumbosacral. For the brainstem region, needle EMG abnormalities are required in only 1 muscle. For the thoracic region, abnormalities can be in the thoracic paraspinal muscles below the T6 level or in the abdominal muscles. For the cervical and lumbosacral paraspinal regions, abnormalities must be present in more than 2 muscles innervated by 2 different nerve roots and peripheral nerves.

Needle examination of the sternocleidomastoid muscles carries a similar sensitivity as examination of the tongue in patients with bulbar symptoms (Li et al 2002).

Neuroimaging of the brain and spinal cord. Neuroimaging is useful in excluding disorders that have symptoms that mimic amyotrophic lateral sclerosis. For example, bulbar palsy may be seen in patients with brainstem glioma, brainstem stroke, multiple sclerosis, and foramen magnum tumor. In these instances, an MRI of the brainstem will show abnormalities. Neoplastic polyradiculopathy, which has abnormal meningeal enhancement in an MRI, may present with clinical and electrodiagnostic test features that mimic progressive muscular atrophy. Spinal cord tumors, transverse myelitis, and spondylotic myelopathy may have upper motor neuron findings that mimic primary lateral sclerosis. MRI of the spinal cord proves useful in differentiating these disorders.

Clinical laboratory testing. Laboratory studies commonly obtained include the following: complete blood count, erythrocyte sedimentation rate, blood chemistry, creatine phosphokinase test, thyroid function test, parathyroid function test, serum rapid plasma reagin test, B12 level, antinuclear antibody test, RA, and serum immunofixation electrophoresis. These studies provide a basic screening for the patient’s general health. In addition, special tests may be ordered to exclude amyotrophic lateral sclerosis-related syndromes. These syndromes have unique laboratory-defined characteristics that are linked to the development of the phenotype. These include amyotrophic lateral sclerosis-related syndromes associated with paraproteinemia, anti-GM1 antibodies, lymphoma, endocrinopathies, infections, toxins, ischemia, and cervical spondylosis. The motor neuron disease associated with anti-GM1 antibodies may have pure lower motor neuron or amyotrophic lateral sclerosis features associated with anti-GM1 antibodies. The amyotrophic lateral sclerosis-related syndrome associated with lymphoma presents with lymphadenopathy (check chest x-ray), monoclonal gammopathy (check immunofixation electrophoresis), increased CSF protein (perform lumbar puncture), and abnormal bone marrow biopsy. If a patient is younger than 40 years of age, the possibility of hexosaminidase A deficiency must be considered. Although many physicians order heavy metal screenings for mercury, lead, and arsenic in blood and urine, there has not been a convincing report of heavy metal-induced motor neuron disease for 25 years (Rowland and Shneider 2001).

Muscle biopsy. Muscle biopsy becomes useful when a confirmation of the neurogenic changes caused by the lower motor neuron degeneration and exclusion of myopathic diseases, such as inclusion body myositis, is necessary.

In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited