What tests are needed to diagnose ALS?

ALS is primarily diagnosed based on physical signs (muscle weakness, muscle atrophy, hyperreflexia, spasticity). In addition to these neurological symptoms, various diagnostic procedures are used to confirm the clinical findings or to rule out the possibility of ALS based on physical findings. The scope of “tests” classified as supplementary examinations is largely determined by the clarity of the neurological symptoms.

When there are clear, ALS-typical findings on examination, the need for additional diagnostic procedures is minimal. The tests serve to confirm and validate the clinical diagnosis. In other situations, the clinical diagnosis may still be inconclusive or uncertain. In such cases, there is a strong need for additional diagnostic testing to rule out neurological disorders that can also cause muscle weakness (paresis), muscle wasting (myopathy), or muscle stiffness (spasticity). Important neurological “tests” include magnetic resonance imaging (MRI) of the brain (cerebral MRI) and the spinal cord (spinal MRI). Additional diagnostic tests may include electromyography (EMG), electroneurography, and laboratory tests, including the biomarker neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF).

Genetic testing has also become more important. It is now recommended for all affected individuals, as certain genetic changes are associated with treatment options. For those with a mutation in the SOD1 gene, there is already an approved treatment with the drug Tofersen. For a mutation in the FUS gene, a Phase 3 trial with a new drug is currently underway. New studies and treatment approaches are also in the works for the genetic forms associated with C9orf72 and TARDBP. This makes testing for the SOD1, C9orf72, FUS, and TARDBP genes particularly important.