Tests
1st tests to order
clinical diagnosis
Test
A thorough history and physical exam are central to the diagnostic process, followed by electrodiagnostic testing when required for additional evidence of occult lower motor neuron involvement.
Result
presence of upper and lower motor neuron signs, disease progression, and absence of any other explanation for the presentation
Tests to consider
electromyography (EMG) and nerve conduction studies
Test
Evidence of diffuse, ongoing (fibrillation potentials and positive waves) and chronic (motor unit potentials with large amplitude and long duration) denervation involving muscles innervated by different nerves or roots in upper limbs, lower limbs (cervical, lumbosacral segments), and thoracic paraspinal muscles or tongue muscle (bulbar).
Can be normal or might show decreased compound motor action potential (CMAP) amplitude, with severe axonal loss.
The presence of severe slowing of motor conduction velocity or the finding of conduction block in motor nerves indicates the presence of an alternative etiology and eliminates ALS as the diagnosis.[39]
The sensory nerve conduction studies should be normal.[40][41]
EMG of clinically unaffected limbs or muscles may demonstrate lower motor neuron disease and be diagnostic in patients whose clinical presentation is limited to one or two limbs.
Result
evidence of diffuse, ongoing, chronic denervation
repetitive nerve stimulation
Test
Rarely indicated, as myasthenia gravis should not be confused with ALS in most situations.
Abnormal in >50% of patients with ALS, but milder abnormalities than typical in myasthenia.
Result
only modest decreases in compound motor action amplitude after repetitive stimuli
MRI brain and spine
Test
In patients without clear bulbar signs, a combination of spinal cord and multiple spinal root compression may resemble ALS; imaging is performed to rule out this possibility.
Result
normal in ALS
anti-GM1 antibodies
Test
GM1 ganglioside antibody titer should be obtained in patients with suspected multifocal mononeuropathy; anti-GM1 antibodies are positive in up to 80% of patients with this condition, although this test does not have a high specificity.[45]
Result
usually negative in ALS
voltage-gated calcium-channel antibodies
Test
To rule out Lambert-Eaton syndrome.
Result
negative in ALS
acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) antibodies
Test
To evaluate for myasthenia gravis.
Result
negative in ALS
vitamin B₁₂
Test
Should be checked when the clinical picture consists of a combination of neuropathy and myelopathy.
Result
normal in ALS
creatine kinase
Test
Consequence of denervated muscles in ALS. Higher levels suggest alternate diagnosis.
Result
might be elevated to maximum of 1000 units/L
lumbar puncture
Test
Rarely necessary. CBC, glucose, protein, cytology.
Result
normal in ALS
HIV test
Test
To consider: HIV testing with a history of exposure.
Result
may be negative or positive
genetic testing
Test
Guidelines recommend that all patients with ALS are offered genetic testing with an ALS gene panel that includes the C9orf72, SOD1, FUS, and TARDBP genes. Additional genetic testing is recommended for genes strongly and definitively associated with ALS as determined by ClinGen, and any gene for which there is an approved gene-targeted therapy.[24]
Genetic counseling and education should be provided for all patients with ALS, and this should precede the offer of testing. Pretest counseling should cover the range of possible testing outcomes, and prepare patients for possible personal, psychological, and economic impacts of testing on themselves and family members, Post-test counseling should also be provided, giving the patients the opportunity to discuss their result and understand the implications for them and their family.[24]
Result
may be positive
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