What is the appropriate workup for Amyotrophic Lateral Sclerosis (ALS)?

From the Guidelines

The workup for Amyotrophic Lateral Sclerosis (ALS) should begin with a thorough neurological examination, followed by MRI head without IV contrast, which is usually appropriate for the initial imaging of patients with suspected motor neuron disease, as recommended by the American College of Radiology 1. The initial evaluation should also include electrodiagnostic studies, such as electromyography (EMG) and nerve conduction studies (NCS), to identify lower motor neuron dysfunction and rule out other conditions.

• Laboratory tests, including complete blood count, comprehensive metabolic panel, thyroid function tests, vitamin B12 levels, serum protein electrophoresis, and inflammatory markers, should be performed to exclude other potential causes of symptoms.
• Genetic testing is recommended for patients with a familial ALS history, particularly for SOD1, C9orf72, FUS, and TARDBP mutations.
• Neuroimaging with MRI of the brain is essential to exclude structural lesions that might mimic ALS, and MRI spine without IV contrast may be appropriate for certain patients with suspected motor neuron disease to exclude structural, infectious, or neoplastic etiologies of the spine 1.
• The most common MRI finding in the brain in ALS is abnormal signal on T2/FLAIR or proton density–weighted images, which can be seen anywhere within the cortico-spinal tracts, and T2*-weighted imaging or susceptibility-weighted imaging can also be useful in the evaluation of suspected ALS 1.
• Pulmonary function tests should be conducted at diagnosis to establish baseline respiratory function, as respiratory failure is a common complication.
• A comprehensive approach, including these tests, allows for accurate diagnosis according to the revised El Escorial criteria, which classify ALS based on the presence of upper and lower motor neuron signs in different body regions, and early diagnosis is crucial as riluzole and edaravone treatments are more effective when started early in the disease course.

From the Research

Diagnostic Workup for Amyotrophic Lateral Sclerosis (ALS)

The diagnostic workup for ALS involves a combination of clinical evaluation and laboratory tests. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used to track its progression 2.

• The El Escorial criteria are used to define the essential requirements for diagnosis of ALS 3.
• Laboratory tests such as electromyography (EMG) and nerve conduction studies can be used to confirm the diagnosis and exclude other diseases 2, 3.
• Imaging studies such as MRI and CT of the spine and brain can also be used to exclude other diseases and confirm the diagnosis 3.
• Genetic testing can identify gene defects in some types of familial ALS and in certain other inherited motor neuron diseases that mimic ALS 3.

Laboratory Tests

Laboratory tests play a crucial role in the diagnosis of ALS.

• EMG and nerve conduction studies are used to assess motor neuron function and can help confirm the diagnosis of ALS 2, 3.
• Biochemical markers in blood and CSF can be used to exclude other diseases and confirm the diagnosis 3.
• Muscle or nerve biopsy can be used to confirm the diagnosis of ALS, although this is not commonly used 3.

Challenges in Diagnosis

Despite the availability of laboratory tests, the diagnosis of ALS can be challenging.

• Physician misdiagnosis of ALS relates to lack of knowledge about ALS and skill and to diagnostic difficulty 3.
• The differential diagnosis must exclude nonmotor neuron diseases and other adult-onset motor neuron diseases with restricted presentations 3.
• Correct and early diagnosis of ALS can only be achieved when the first, second, or third physician who sees the patient knows about ALS and includes it in a differential diagnosis 3.