Conclusions

This systematic review and meta-analysis demonstrates that bulbar-onset ALS is diagnosed approximately 4 months earlier than limb-onset ALS, a finding consistent across studies from eight countries and robust to leave-one-out analysis. These findings derive predominantly from retrospective observational studies and should be interpreted alongside the very low GRADE certainty rating, which reflects uncertainty in the precise magnitude of the delay rather than its direction. Given that total survival in ALS is measured in months, this differential is clinically significant. The results support targeted awareness strategies directed at the clinicians most likely to encounter limb-onset presentations, including primary care physicians, orthopedic surgeons, and spine specialists, to reduce diagnostic delay and maximize the therapeutic window for available treatments.