Diagnosing ALS remains challenging due to the lack of definitive biomarkers, prompting the development of clinical criteria, such as the EEC, its revisions, and later the AC. However, these criteria showed high specificity but low sensitivity. In 2020, the GCC were introduced to simplify diagnosis and improve early-stage sensitivity.

We performed a systematic literature search in PubMed-MEDLINE, EMBASE, and Cochrane databases until September 2024. We focused on studies comparing GCC with rEEC and/or AC in the entire study population to minimize heterogeneity. We defined "possible+" which includes possible, probable, and definite categories for AC, and possible, probable, probable laboratory-supported and definite for rECC. “Probable+” includes probable and definite categories for AC, and probable, probable laboratory-supported and definite for rECC. Summary receiver operating characteristic (sROC) curves were constructed, and areas under the curve (AUCs) were calculated.

Four studies met inclusion criteria, comprising 2696 patients. SROC curves for GCC showed superior sensitivity 94.3% (95%CI:0.903, 0.967) with specificity 82.4% (95%CI:0.353, 0.976). AC “possible+” category demonstrated a pooled sensitivity 86.6% (95%CI:0.821, 0.901) and specificity 84.3% (95%CI:0.454, 0.972). AC “probable+” category exhibited lower sensitivity 55.8% (95%CI:0.456, 0.655) but high specificity 99.0% (95%CI:0.639, 1.0). And rEEC “possible+” category had a sensitivity 85.7% (95%CI:0.811, 0.892) and specificity 85.0% (95%CI:0.459, 0.974), while rEEC “probable+” category reflected sensitivity 59.6% (95%CI:0.457, 0.720) and specificity 99.0% (95%CI:0.505, 1.0).