Table 1.

The ideal characteristics of a biomarker in ALS.

1. Sensitive and specific for the heterogeneous syndrome of ALS

2. Detectable prior to the onset of significant wasting/weakness

3. Discriminate between clinical phenotypes based on: a) Upper and lower motor neuron involvement e.g. PMA and PLS b) Patterns of regional involvement e.g. flail arm/leg, PBP c) Cognitive involvement i.e. ALS-MCI versus ALS-FTD d) Extremes of survival i.e. ‘aggressive’ (1-2 year survival from symptom onset) versus ‘slow’ (5-10 year) course

4. Able to predict regional involvement and the pattern of spread in advance: a) Bulbar dysfunction for early PEG b) Respiratory dysfunction for early NIV (possibly diaphragm pacing) c) Cognitive impairment

5. Change in a predictable way with disease progression

6. Sensitivity to confidently judge therapeutic response within weeks of challenge

7. Easily accessible and affordable technology

8. Practical to measure in the physically disabled patient